International review of neurobiology最新文献

Stress is one of the most serious consequences of life leading to several chronic diseases and neurodegeneration. Recent studies show that emotional stress and other kinds of anxiety and depression adversely affects Parkinson's disease symptoms. However, the details of how stress affects Parkinson's disease is still not well known. Traumatic brain injury, stroke, diabetes, post-traumatic stress disorders are well known to modify the disease precipitation, progression and persistence. However, show stress could influence Parkinson's disease is still not well known. The present investigation we examine the role of immobilization stress influencing Parkinson's disease brain pathology in model experiments. In ore previous report we found that mild traumatic brain injury exacerbate Parkinson's disease brain pathology and nanodelivery of dl-3-n-butylphthalide either alone or together with mesenchymal stem cells significantly attenuated Parkinson's disease brain pathology. In this chapter we discuss the role of stress in exacerbating Parkinson's disease pathology and nanowired delivery of dl-3-n-butylphthalide together with monoclonal antibodies to alpha synuclein (ASNC) is able to induce significant neuroprotection. The possible mechanisms of dl-3-n-butylphthalide and ASNC induced neuroprotection and suitable clinical therapeutic strategy is discussed.

Adenosine, a known endogenous somnogen, induces sleep via A₁ and A_2A receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A_2A receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A_2A receptor agonists, antagonists, and allosteric modulators have been identified, only a few have been tested to see if they can promote sleep or wakefulness. In addition, the growing popularity of natural sleep aids has led to an investigation of natural compounds that may improve sleep by activating the adenosine A_2A receptor. Finally, we discuss the potential therapeutic advantage of allosteric modulators of adenosine A_2A receptors over classic agonists and antagonists for treating sleep and neurologic disorders.

Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed.

Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including, antineoplastic, antioxidative and neuroprotective effects. Recent studies provided evidence for the bioactive role of curcumin in the prevention and treatment of various central nervous system (CNS)-related diseases including Parkinson's, Alzheimer's, Schizophrenia disease and glioma neoplasia. Schizophrenia is a disabling psychiatric disorder related with an aberrant functional coupling between hippocampus and prefrontal cortex that might be crucial for cognitive dysfunction. Animal studies have lent support to the hypothesis that curcumin could improve cognitive functioning and enhance cell proliferation of dentate gyrus. In relation to brain tumors, specifically gliomas, the antineoplastic action of curcumin is based on the inhibition of cell growth promoting apoptosis or autophagy and preventing angiogenesis. However, one of the main impediments for the application of curcumin to patients is its low bioavailability. In intracranial lesions, curcumin has problems to cross the blood-brain barrier (BBB). Currently nano-based drug delivery systems are opening a new horizon to tackle this problem. The bioavailability and effective release of curcumin can be made possible in the form of nanocurcumin. This nanoformulation preserves the properties of curcumin and makes it reach tissues with pathology. This review try to study the beneficial effects of the curcumin nanodelivery in central nervous pathologies such us schizophrenia and glioma disease.

Although there is no cure for Parkinson's disease (PD), there are several classes of medications with various mechanisms of action that can help improve the functionality of someone with PD. Dopamine derivatives are first line therapies for PD, hence dopamine receptor agonists (DAs) have been shown to improve functionality of symptoms in PD patients. The two main formulations of dopamine agonist medications in PD therapy are ergoline and non-ergoline derivatives. Additionally, it has been shown that PD can involve irregularities in other neurotransmitters, such as acetylcholine, norepinephrine, and serotonin, hence why non-dopaminergic medications are also vital in PD management. Examples include NMDA receptor antagonists, dopamine antagonists (i.e. neuroleptics), acetylcholine receptor antagonists, serotonin receptor 2A agonists, and adenosine A₂ antagonists. In general, dopaminergic medications are the most effective in improving motor involvement with PD, whereas non-dopaminergic medications tend to focus on the non-motor involvement of PD. In this chapter, we will focus on the chemistry and medication background on dopaminergic vs non-dopaminergic therapy, with a focus of adenosine A₂ antagonists at the end.

Sleep deprivation is quite frequent in military during combat, intelligence gathering or peacekeeping operations. Even one night of sleep deprivation leads to accumulation of amyloid beta peptide burden that would lead to precipitation of Alzheimer's disease over the years. Thus, efforts are needed to slow down or neutralize accumulation of amyloid beta peptide (AβP) and associated Alzheimer's disease brain pathology including phosphorylated tau (p-tau) within the brain fluid environment. Sleep deprivation also alters serotonin (5-hydroxytryptamine) metabolism in the brain microenvironment and impair upregulation of several neurotrophic factors. Thus, blockade or neutralization of AβP, p-tau and serotonin in sleep deprivation may attenuate brain pathology. In this investigation this hypothesis is examined using nanodelivery of cerebrolysin- a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies against AβP, p-tau and serotonin (5-hydroxytryptamine, 5-HT). Our observations suggest that sleep deprivation induced pathophysiology is significantly reduced following nanodelivery of cerebrolysin together with monoclonal antibodies to AβP, p-tau and 5-HT, not reported earlier.

Accumulating evidence has revealed the adenosine 2A receptor is a key tuner for neuropathological and neurobehavioral changes following traumatic brain injury by experimental animal models and a few clinical trials. Here, we highlight recent data involving acute/sub-acute and chronic alterations of adenosine and adenosine 2A receptor-associated signaling in pathological conditions after trauma, with an emphasis of traumatic brain injury, including neuroinflammation, cognitive and psychiatric disorders, and other severe consequences. We expect this would lead to the development of therapeutic strategies for trauma-related disorders with novel mechanisms of action.

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.

dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AβP) inactivating enzyme neprilysin. We have used TiO₂ nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature.

Adenosine is a neuroregulatory nucleoside that acts through four G protein-coupled receptors (GPCRs), A₁, A_2A, A_2B and A₃, which are widely expressed in cells of the nervous system. The A_2A receptor (A_2AR), the GPCR with the highest expression in the striatum, has a similar role to that of receptors for dopamine, one of the main neurotransmitters. Neuronal and glial A_2ARs participate in the modulation of dopaminergic transmission and act in almost any action in which the basal ganglia is involved. This chapter revisits the expression of the A_2AR in the basal ganglia in health and disease, and describes the diversity of signalling depending on whether the receptors are expressed as monomer or as heteromer. The A_2AR can interact with other receptors as adenosine A₁, dopamine D₂, or cannabinoid CB₁ to form heteromers with relevant functions in the basal ganglia. Heteromerization, with these and other GPCRs, provides diversity to A_2AR-mediated signalling and to the modulation of neurotransmission. Thus, selective A_2AR antagonists have neuroprotective potential acting directly on neurons, but also through modulation of glial cell activation, for example, by decreasing neuroinflammatory events that accompany neurodegenerative diseases. In fact, A_2AR antagonists are safe and their potential in the therapy of Parkinson's disease has already led to the approval of one of them, istradefylline, in Japan and United States. The receptor also has a key role in reward circuits and, again, heteromers with dopamine receptors, but also with cannabinoid CB₁ receptors, participate in the events triggered by drugs of abuse.