Neuroscience Letters最新文献

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Inhibition of the TRPM2 cation channel attenuates morphine tolerance by modulating endoplasmic reticulum stress and apoptosis in rats

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-18 DOI: 10.1016/j.neulet.2025.138168

Arzuhan Cetindag Ciltas , Ercan Ozdemir , Handan Gunes , Aysegul Ozturk

Opioid drugs such as morphine are frequently preferred drugs for severe pain in cancer and chronic diseases, but long-term use causes opioid tolerance. The mechanism of tolerance to opioids is quite complex and not fully understood. Our aim in this study was to investigate the effects of TRPM2 cation channel antagonists N-(p-amylcinnamoyl) anthranilic acid (ACA) and 2-aminoethoxydiphenyl borate (2-APB) on morphine analgesia and tolerance in rats. Forty-eight Wistar Albino male rats were included in the study and the rats were randomly divided into drug and control (saline) groups. To induce morphine tolerance, the rats were injected with 10 mg/kg morphine intraperitoneally for 7 days. After thermal analgesia tests, dorsal root ganglion (DRG) and cortex tissues were isolated. Proapoptotic mediators caspase-3 and 9, total oxidant status (TOS) and total antioxidant status (TAS) and ER stress proteins GRP78/BiP, ATF-6, p-IRE1 and pERK levels were measured by biochemical analysis of tissue homogenates. The findings showed that there was a significant decrease in morphine tolerance in rats administered ACA and 2-APB (p<0.05). In addition, biochemical tests revealed a significant decrease in ER stress proteins, proapoptotic biomarkers and TOS levels and a significant increase in TAS levels in DRG, thalamus and sensory cortex tissues (p<0.05). In conclusion, inhibition of TRPM2 cation channel by ACA and 2-APB reduces morphine tolerance by preventing ER stress and apoptosis. It may be possible to increase the analgesic potential of morphine by combined application with ACA and 2-APB in the clinic, but further experimental and molecular studies are needed.

{"title":"Inhibition of the TRPM2 cation channel attenuates morphine tolerance by modulating endoplasmic reticulum stress and apoptosis in rats","authors":"Arzuhan Cetindag Ciltas , Ercan Ozdemir , Handan Gunes , Aysegul Ozturk","doi":"10.1016/j.neulet.2025.138168","DOIUrl":"10.1016/j.neulet.2025.138168","url":null,"abstract":"<div><div>Opioid drugs such as morphine are frequently preferred drugs for severe pain in cancer and chronic diseases, but long-term use causes opioid tolerance. The mechanism of tolerance to opioids is quite complex and not fully understood. Our aim in this study was to investigate the effects of TRPM2 cation channel antagonists N-(p-amylcinnamoyl) anthranilic acid (ACA) and 2-aminoethoxydiphenyl borate (2-APB) on morphine analgesia and tolerance in rats. Forty-eight Wistar Albino male rats were included in the study and the rats were randomly divided into drug and control (saline) groups. To induce morphine tolerance, the rats were injected with 10 mg/kg morphine intraperitoneally for 7 days. After thermal analgesia tests, dorsal root ganglion (DRG) and cortex tissues were isolated. Proapoptotic mediators caspase-3 and 9, total oxidant status (TOS) and total antioxidant status (TAS) and ER stress proteins GRP78/BiP, ATF-6, p-IRE1 and pERK levels were measured by biochemical analysis of tissue homogenates. The findings showed that there was a significant decrease in morphine tolerance in rats administered ACA and 2-APB (p<0.05). In addition, biochemical tests revealed a significant decrease in ER stress proteins, proapoptotic biomarkers and TOS levels and a significant increase in TAS levels in DRG, thalamus and sensory cortex tissues (p<0.05). In conclusion, inhibition of TRPM2 cation channel by ACA and 2-APB reduces morphine tolerance by preventing ER stress and apoptosis. It may be possible to increase the analgesic potential of morphine by combined application with ACA and 2-APB in the clinic, but further experimental and molecular studies are needed.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138168"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between individual differences in gait motor imagery and visuo-spatial working memory after stroke

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-17 DOI: 10.1016/j.neulet.2025.138167

Kohei Kotegawa , Naoki Kuroda , Junya Sakata , Ren Fujii , Wataru Teramoto

Motor imagery is a mental process in which an individual internally simulates movements without actual motor execution. Gait motor imagery is associated with visuospatial working memory (VSWM) among young adults. This study investigates how individual differences in gait motor imagery ability among stroke patients are related to VSWM. Gait motor imagery of 12 S patients with right hemisphere damage and 12 healthy older adults were evaluated and compared in this study. Gait motor imagery ability was evaluated by comparing actual and mental walking times while manipulating path width, whereas VSWM ability was evaluated using the Corsi Block-Tapping task. The results revealed that VSWM ability could predict the accuracy of gait motor imagery for both stroke patients and healthy controls; those with higher VSWM ability exhibited more overestimation of mental walking time over actual walking time. Additionally, based on the results of dividing stroke participants into two groups depending on whether they had right prefrontal cortex (PFC) damage, stroke patients with right PFC damage had decreased VSWM, and underestimated mental walking over actual walking for all path widths compared to those with non-right PFC damage. These results suggest that gait motor imagery accuracy is associated with individual differences in VSWM ability, particularly in patients affected by right PFC damage.

{"title":"Association between individual differences in gait motor imagery and visuo-spatial working memory after stroke","authors":"Kohei Kotegawa , Naoki Kuroda , Junya Sakata , Ren Fujii , Wataru Teramoto","doi":"10.1016/j.neulet.2025.138167","DOIUrl":"10.1016/j.neulet.2025.138167","url":null,"abstract":"<div><div>Motor imagery is a mental process in which an individual internally simulates movements without actual motor execution. Gait motor imagery is associated with visuospatial working memory (VSWM) among young adults. This study investigates how individual differences in gait motor imagery ability among stroke patients are related to VSWM. Gait motor imagery of 12 S patients with right hemisphere damage and 12 healthy older adults were evaluated and compared in this study. Gait motor imagery ability was evaluated by comparing actual and mental walking times while manipulating path width, whereas VSWM ability was evaluated using the Corsi Block-Tapping task. The results revealed that VSWM ability could predict the accuracy of gait motor imagery for both stroke patients and healthy controls; those with higher VSWM ability exhibited more overestimation of mental walking time over actual walking time. Additionally, based on the results of dividing stroke participants into two groups depending on whether they had right prefrontal cortex (PFC) damage, stroke patients with right PFC damage had decreased VSWM, and underestimated mental walking over actual walking for all path widths compared to those with non-right PFC damage. These results suggest that gait motor imagery accuracy is associated with individual differences in VSWM ability, particularly in patients affected by right PFC damage.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138167"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deletion of filamin A-interacting protein (FILIP) results in a weak grip strength and abnormal responses to nociceptive stimulation

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-15 DOI: 10.1016/j.neulet.2025.138158

Hideshi Yagi , Keizo Takao , Satoko Hattori , Yusuke Minato , Sachi Kuwahara-Otani , Seishi Maeda , Koichi Noguchi , Tsuyoshi Miyakawa , Makoto Sato

Filamin A-interacting protein (FILIP in mice, FILIP1 in humans) was first identified as a protein that negatively controls neuronal migration in rodents, and was subsequently demonstrated to be pivotal for the development of the neocortex. In the previous study, we generated FILIP knockout mice to investigate the in vivo functions of FILIP in cortical development. Since FILIP mRNA is widely expressed in the body, we systematically examined FILIP-knockout mice to determine the functions of FILIP throughout the body. Our results showed that FILIP-knockout mice exhibited weak grip strength and sensory abnormalities. Interestingly, we also found that FILIP was expressed in a subset of neurons in the dorsal root ganglion (DRG). Recent research has reported that FILIP1 mutations lead to severe neurological and musculoskeletal abnormalities, resulting in the proposal of a new disease entity, termed FILIP1opathy. It is expected that our FILIP-knockout mice could be used as a model for the pathological investigation of FILIP1opathy.

{"title":"Deletion of filamin A-interacting protein (FILIP) results in a weak grip strength and abnormal responses to nociceptive stimulation","authors":"Hideshi Yagi , Keizo Takao , Satoko Hattori , Yusuke Minato , Sachi Kuwahara-Otani , Seishi Maeda , Koichi Noguchi , Tsuyoshi Miyakawa , Makoto Sato","doi":"10.1016/j.neulet.2025.138158","DOIUrl":"10.1016/j.neulet.2025.138158","url":null,"abstract":"<div><div>Filamin A-interacting protein (FILIP in mice, FILIP1 in humans) was first identified as a protein that negatively controls neuronal migration in rodents, and was subsequently demonstrated to be pivotal for the development of the neocortex. In the previous study, we generated FILIP knockout mice to investigate the in vivo functions of FILIP in cortical development. Since FILIP mRNA is widely expressed in the body, we systematically examined FILIP-knockout mice to determine the functions of FILIP throughout the body. Our results showed that FILIP-knockout mice exhibited weak grip strength and sensory abnormalities. Interestingly, we also found that FILIP was expressed in a subset of neurons in the dorsal root ganglion (DRG). Recent research has reported that <em>FILIP1</em> mutations lead to severe neurological and musculoskeletal abnormalities, resulting in the proposal of a new disease entity, termed FILIP1opathy. It is expected that our FILIP-knockout mice could be used as a model for the pathological investigation of FILIP1opathy.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138158"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of opioid receptors in the anti-allodynic effect of local montelukast in a rat chronic constriction injury of sciatic nerve model

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-15 DOI: 10.1016/j.neulet.2025.138165

Behnam Ghorbanzadeh , Behnam Azizolahi , Mohammad Amin Behmanesh , Parsa Forouhar , Ali Foroughinia , Mohadeseh Nabizadeh

Neuropathic pain is a debilitating and chronic condition that results from damage to the peripheral and central nervous system. The inflammatory mediators such as leukotrienes, and opioidergic pathways are involved in the neuropathic pain generation. The present study aimed to determine the effect of local montelukast and the role of opioid receptors using chronic constriction injury (CCI) of the sciatic nerve in rats. Our results showed that montelukast (1–10 mcg/paw) or morphine (1 and 10 mcg/paw) attenuated the mechanical and cold allodynia at day 7 and 14 post-CCI. The effect of montelukast was attenuated by local pre-treatment with naloxone (20 mcg/paw), and was augmented by an ineffective dose of morphine. Also, the histopathological investigation showed the peripheral anti-inflammatory effect of montelukast in the sciatic-injured paw. Moreover, spinal cord mu-opioid receptor mRNA decreased, and kappa-opioid receptor mRNA increased in rats 14 days after CCI by RT-PCR analyses. However, the administration of montelukast on days 7 and 14 after CCI reversed the observed changes in opioid receptors. Our findings suggested that local montelukast can attenuate neuropathic pain, at least in part, through the peripheral opioid receptors, peripheral anti-inflammatory, and also spinal mu- and kappa-opioid receptors. So, local montelukast could be a novel therapeutic strategy for alleviating neuropathic pain.

{"title":"The role of opioid receptors in the anti-allodynic effect of local montelukast in a rat chronic constriction injury of sciatic nerve model","authors":"Behnam Ghorbanzadeh , Behnam Azizolahi , Mohammad Amin Behmanesh , Parsa Forouhar , Ali Foroughinia , Mohadeseh Nabizadeh","doi":"10.1016/j.neulet.2025.138165","DOIUrl":"10.1016/j.neulet.2025.138165","url":null,"abstract":"<div><div>Neuropathic pain is a debilitating and chronic condition that results from damage to the peripheral and central nervous system. The inflammatory mediators such as leukotrienes, and opioidergic pathways are involved in the neuropathic pain generation. The present study aimed to determine the effect of local montelukast and the role of opioid receptors using chronic constriction injury (CCI) of the sciatic nerve in rats. Our results showed that montelukast (1–10 mcg/paw) or morphine (1 and 10 mcg/paw) attenuated the mechanical and cold allodynia at day 7 and 14 post-CCI. The effect of montelukast was attenuated by local pre-treatment with naloxone (20 mcg/paw), and was augmented by an ineffective dose of morphine. Also, the histopathological investigation showed the peripheral anti-inflammatory effect of montelukast in the sciatic-injured paw. Moreover, spinal cord mu-opioid receptor mRNA decreased, and kappa-opioid receptor mRNA increased in rats 14 days after CCI by RT-PCR analyses. However, the administration of montelukast on days 7 and 14 after CCI reversed the observed changes in opioid receptors. Our findings suggested that local montelukast can attenuate neuropathic pain, at least in part, through the peripheral opioid receptors, peripheral anti-inflammatory, and also spinal mu- and kappa-opioid receptors. So, local montelukast could be a novel therapeutic strategy for alleviating neuropathic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138165"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic anxiolytic-like effect of CPPG and harmaline in non-stressed and acute restraint stress (ARS) mice

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-10 DOI: 10.1016/j.neulet.2025.138157

Nazahnin Hasan-Kareem , Sakineh Alijanpour , Mohammad-Reza Zarrindast , Fatemeh Khakpai

Many studies revealed the role of metabotropic glutamate receptors (mGluRs) and harmaline in the modulation of anxiety-related behaviors. This study aimed to determine a possible interaction between harmaline and group III mGluR on the modulation of anxiety-correlated behaviors. The left lateral ventricle of male mice was unilaterally cannulated. Acute restraint stress (ARS) was induced by movement restraint for 4 h. Anxiety-like behaviors were measured using an elevated plus maze. The results showed that induction of ARS during 4 h reduced the percentage of time spent in open arms (%OAT) and percentage of entries to open arms (%OAE) without changing locomotor activity, indicating anxiogenic-like responses. Intraperitoneal (i.p.) administration of harmaline (2 mg/kg) increased %OAT in non-stressed and ARS mice, presenting anxiolytic-like responses. Intracerebroventricular (i.c.v.) infusion of CPPG (potent group III mGlu antagonist, 70 µg/mouse) induced anxiolytic-like behavior due to the augmentation of %OAT in non-stressed and ARS mice. Co-treatment of CPPG (70 µg/mouse, i.c.v.) along with harmaline (1 mg/kg, i.p) induced an anxiolytic-like effect. I.c.v. infusion of L-AP4 (selective group III mGlu agonist) or co-administration of it along harmaline had no significant effect on anxiety-like behaviors both in non-stressed and ARS mice. When harmaline and CPPG were co-administrated, CPPG potentiated the anxiolytic-like behavior induced by harmaline in non-stressed and ARS mice. The results revealed a synergistic effect between CPPG and harmaline on the induction of anxiolytic-like effect in non-stressed and ARS mice. Our results indicated an interaction between harmaline and group III mGluR on the modulation of anxiety-like responses in non-stressed and ARS mice.

{"title":"Synergistic anxiolytic-like effect of CPPG and harmaline in non-stressed and acute restraint stress (ARS) mice","authors":"Nazahnin Hasan-Kareem , Sakineh Alijanpour , Mohammad-Reza Zarrindast , Fatemeh Khakpai","doi":"10.1016/j.neulet.2025.138157","DOIUrl":"10.1016/j.neulet.2025.138157","url":null,"abstract":"<div><div>Many studies revealed the role of metabotropic glutamate receptors (mGluRs) and harmaline in the modulation of anxiety-related behaviors. This study aimed to determine a possible interaction between harmaline and group III mGluR on the modulation of anxiety-correlated behaviors. The left lateral ventricle of male mice was unilaterally cannulated. Acute restraint stress (ARS) was induced by movement restraint for 4 h. Anxiety-like behaviors were measured using an elevated plus maze. The results showed that induction of ARS during 4 h reduced the percentage of time spent in open arms (%OAT) and percentage of entries to open arms (%OAE) without changing locomotor activity, indicating anxiogenic-like responses. Intraperitoneal (i.p.) administration of harmaline (2 mg/kg) increased %OAT in non-stressed and ARS mice, presenting anxiolytic-like responses. Intracerebroventricular (i.c.v.) infusion of CPPG (potent group III mGlu antagonist, 70 µg/mouse) induced anxiolytic-like behavior due to the augmentation of %OAT in non-stressed and ARS mice. Co-treatment of CPPG (70 µg/mouse, i.c.v.) along with harmaline (1 mg/kg, i.p) induced an anxiolytic-like effect. I.c.v. infusion of L-AP4 (selective group III mGlu agonist) or co-administration of it along harmaline had no significant effect on anxiety-like behaviors both in non-stressed and ARS mice. When harmaline and CPPG were co-administrated, CPPG potentiated the anxiolytic-like behavior induced by harmaline in non-stressed and ARS mice. The results revealed a synergistic effect between CPPG and harmaline on the induction of anxiolytic-like effect in non-stressed and ARS mice. Our results indicated an interaction between harmaline and group III mGluR on the modulation of anxiety-like responses in non-stressed and ARS mice.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138157"},"PeriodicalIF":2.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of STAT1 improved learning and memory impairments in aging mice

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-09 DOI: 10.1016/j.neulet.2025.138155

Xiao Li , Yao Xu , Ting Li , Bocheng Xiong , Xifei Yang , Yan Feng

Cognitive impairment is a typical hallmark of aging in mice and humans. Here, we reported that downregulation of STAT1 improved learning and memory impairments in aging mice by enhancing the expression of synaptic protein and inhibiting the expression of inflammatory factors. Proteomic analysis revealed 139 differentially expressed proteins (DEPs) in the hippocampus of downregulated-STAT1 aging mice, compared with aging control mice. Functional classification of DEPs indicated that these mainly involved in inflammation, autophagy, synapse, mitochondria and apoptosis. The ClueGo analysis uncovered that the Wiki pathway of these DEPs were involved in proteasome degradation, IL-6 signaling pathway, signaling of hepatocyte growth factor receptor and so on. Taken together, downregulation of STAT1 may delay aging with multiple mechanisms.

引用次数: 0

Dendritic phenotype and proliferation potency in the hippocampal dentate gyrus of the Ts66Yah model of Down syndrome

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-08 DOI: 10.1016/j.neulet.2025.138156

Marco Emili , Fiorenza Stagni , Sandra Guidi , Carla Russo , Claire Chevalier , Arnaud Duchon , Yann Herault , Renata Bartesaghi

The Ts65Dn mouse is the most widely used model of Down syndrome (DS), although, in addition to the triplication of 90 genes homologous to Human Chromosome 21 (Hsa21) genes, it bears the triplication of 46 extra genes. To clarify the latter’s impact, the Ts66Yah model has been created from the Ts65Dn mouse by exploiting CRISPR/Cas9 technology for extra gene deletion. It has been found that, similar to the Ts65Dn model, the Ts66Yah model exhibits impairment in hippocampus-dependent learning and memory and age-related hippocampal deterioration, with no increased activity. We examine here the dendritic development of the hippocampal granule neurons and the proliferation potency of granule cell precursors in Ts66Yah mice because these phenotypes are impaired in Ts65Dn mice and individuals with DS starting from early life stages and are thought to underpin cognitive impairment. In Ts66Yah mice aged 15 days and those aged three months, we found no reduction in dendritic arborization, dendritic spine density, proliferation potency, or total number of granule cells, suggesting that other mechanisms may underpin the behavioral impairment found in the Ts66Yah model in adulthood. Thus, the Ts66Yah model is unsuitable to study these neurodevelopmental alterations, although it may be useful to study other DS-related phenotypes.

{"title":"Dendritic phenotype and proliferation potency in the hippocampal dentate gyrus of the Ts66Yah model of Down syndrome","authors":"Marco Emili , Fiorenza Stagni , Sandra Guidi , Carla Russo , Claire Chevalier , Arnaud Duchon , Yann Herault , Renata Bartesaghi","doi":"10.1016/j.neulet.2025.138156","DOIUrl":"10.1016/j.neulet.2025.138156","url":null,"abstract":"<div><div>The Ts65Dn mouse is the most widely used model of Down syndrome (DS), although, in addition to the triplication of 90 genes homologous to Human Chromosome 21 (Hsa21) genes, it bears the triplication of 46 extra genes. To clarify the latter’s impact, the Ts66Yah model has been created from the Ts65Dn mouse by exploiting CRISPR/Cas9 technology for extra gene deletion. It has been found that, similar to the Ts65Dn model, the Ts66Yah model exhibits impairment in hippocampus-dependent learning and memory and age-related hippocampal deterioration, with no increased activity. We examine here the dendritic development of the hippocampal granule neurons and the proliferation potency of granule cell precursors in Ts66Yah mice because these phenotypes are impaired in Ts65Dn mice and individuals with DS starting from early life stages and are thought to underpin cognitive impairment. In Ts66Yah mice aged 15 days and those aged three months, we found no reduction in dendritic arborization, dendritic spine density, proliferation potency, or total number of granule cells, suggesting that other mechanisms may underpin the behavioral impairment found in the Ts66Yah model in adulthood. Thus, the Ts66Yah model is unsuitable to study these neurodevelopmental alterations, although it may be useful to study other DS-related phenotypes.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138156"},"PeriodicalIF":2.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of kratom alkaloids on mesolimbic dopamine release

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-07 DOI: 10.1016/j.neulet.2025.138153

James P. Manus , Rebecca C. Crenshaw , Lindsay C. Ringer , Shelby A. Towers , Nick B. Paige , Francisco Leon , Christopher R. McCurdy , Deranda B. Lester

Kratom is derived from the leaves of a plant (Mitragyna speciosa) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom’s alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.

{"title":"Effects of kratom alkaloids on mesolimbic dopamine release","authors":"James P. Manus , Rebecca C. Crenshaw , Lindsay C. Ringer , Shelby A. Towers , Nick B. Paige , Francisco Leon , Christopher R. McCurdy , Deranda B. Lester","doi":"10.1016/j.neulet.2025.138153","DOIUrl":"10.1016/j.neulet.2025.138153","url":null,"abstract":"<div><div>Kratom is derived from the leaves of a plant (<em>Mitragyna speciosa</em>) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom’s alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138153"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of fatty acids on glutamate-related gene expression in the hippocampus: Focus on lauric acid

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-07 DOI: 10.1016/j.neulet.2025.138152

Laura Romero-Muñoz , Ana Belén Sanz-Martos , Nuria Del Olmo , Beatriz Merino , Mariano Ruiz-Gayo , Victoria Cano

Excessive dietary fat consumption has been linked to impairments in synaptic plasticity in the hippocampus (HIP), a brain region crucial for learning and memory that relies on balanced glutamatergic neurotransmission. This study investigates the acute effects of three fatty acids (FAs)—lauric acid (LA), palmitic acid (PA), and oleic acid (OA)—on glutamate (GLU)-related gene expression in the HIP of male and female young mice. Hippocampal slices were treated with FAs, and mRNA levels of genes involved in GLU transport, GLU-glutamine (GLN) cycling, and GLU receptor subunit encoding were quantified using RT-PCR. FA treatment reduced mRNA levels of enzymes involved in the conversion of GLU to GLN (glutamine synthetase; GS), GABA (glutamate decarboxylase 1; GAD67), and α-ketoglutarate (glutamate pyruvate transaminase 2; AAT2). Additionally, the expression of glutamine transporters (SNAT1, SNAT2, SNAT3), the astrocytic GLU transporter GLT-1, and the NMDA receptor subunit NMDA2a was also reduced. These effects were most pronounced with LA. Notably, while the HIP showed similar sensitivity to fatty acids across sexes, overall gene expression levels were lower in females. These findings highlight the acute susceptibility of hippocampal GLU-related pathways to FA exposure, particularly LA, suggesting potential risks of high-LA diets on cognitive function. Further research is needed to explore the long-term consequences of dietary fat on hippocampal health and its sex-specific effects.

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引用次数: 0

Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-07 DOI: 10.1016/j.neulet.2025.138154

Peng Huang, Conrad K. Ho, Kathryn Bland, Lee-Yuan Liu-Chen

We previously demonstrated that in a mouse line expressing a kappa opioid receptor (KOR) mutant with all the four phosphorylation sites mutated to alanines (K4A) the selective KOR agonist U50,488H (U50)-induced anti-scratching tolerance was attenuated in males and conditioned place aversion (CPA) was reduced in females, without affecting acute U50-induced anti-scratching effect and hypo-locomotion (Huang et al, 2022, Neuropharmacology). KOR phosphorylation deficiency in K4A mice would lead to little recruitment of β-arrestin2 (arrb2) and hence greatly reduced arrb2-mediated KOR regulation, downstream signaling and behaviors. Herein we examined effects of arrb2 deletion in mice on KOR-mediated behaviors in arrb2 knockout (arrb2(-/-)) mice vs wildtype (WT) mice. We found that arrb2 deletion enhanced anti-scratching effects produced by acute U50 in males, but not in females. Intriguingly, in ovariectomized (OVX) but not sham-operated females, arrb2 deletion increased U50-induced anti-scratching effect, similar to males. Furthermore, OVX enhanced U50-induced anti-scratching effects specifically in arrb2(-/-) females, but not in WT females. Thus, ovarian hormones-related modulations may obscure the phenotype associated with arrb2(-/-) to promote the KOR-mediated anti-scratching signaling in females, while OVX unmasked it. In contrast, arrb2 deletion did not affect U50-induced CPA and had no effects on anti-scratching tolerance to repeated U50 in either male or female mice. The findings in arrb2(-/-) mice revealed both similarities and differences compared to our previous results in K4A mice. Overall, the effects of arrb2 deletion on KOR-mediated behaviors depended on specific behavioral endpoints, sex, and OVX status.

{"title":"Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints","authors":"Peng Huang, Conrad K. Ho, Kathryn Bland, Lee-Yuan Liu-Chen","doi":"10.1016/j.neulet.2025.138154","DOIUrl":"10.1016/j.neulet.2025.138154","url":null,"abstract":"<div><div>We previously demonstrated that in a mouse line expressing a kappa opioid receptor (KOR) mutant with all the four phosphorylation sites mutated to alanines (K4A) the selective KOR agonist U50,488H (U50)-induced anti-scratching tolerance was attenuated in males and conditioned place aversion (CPA) was reduced in females, without affecting acute U50-induced anti-scratching effect and hypo-locomotion (Huang et al, 2022, Neuropharmacology). KOR phosphorylation deficiency in K4A mice would lead to little recruitment of β-arrestin2 (arrb2) and hence greatly reduced arrb2-mediated KOR regulation, downstream signaling and behaviors. Herein we examined effects of arrb2 deletion in mice on KOR-mediated behaviors in arrb2 knockout (arrb2(-/-)) mice vs wildtype (WT) mice. We found that arrb2 deletion enhanced anti-scratching effects produced by acute U50 in males, but not in females. Intriguingly, in ovariectomized (OVX) but not sham-operated females, arrb2 deletion increased U50-induced anti-scratching effect, similar to males. Furthermore, OVX enhanced U50-induced anti-scratching effects specifically in arrb2(-/-) females, but not in WT females. Thus, ovarian hormones-related modulations may obscure the phenotype associated with arrb2(-/-) to promote the KOR-mediated anti-scratching signaling in females, while OVX unmasked it. In contrast, arrb2 deletion did not affect U50-induced CPA and had no effects on anti-scratching tolerance to repeated U50 in either male or female mice. The findings in arrb2(-/-) mice revealed both similarities and differences compared to our previous results in K4A mice. Overall, the effects of arrb2 deletion on KOR-mediated behaviors depended on specific behavioral endpoints, sex, and OVX status.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138154"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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