Neuroscience bulletin最新文献

Clinical investigations have suggested a potential link between cataracts and Alzheimer's disease (AD). However, whether cataract has an impact on the progression of AD remains unclear. The objective of this research was to determine the relationship between cataracts and AD. A cataract model was established in APP/PS1 [mutant amyloid precursor protein (APP) and a mutant presenilin-1 (PS1) gene] mice via lens puncture. Behavioural assays were used to evaluate cognitive function. Immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assays (ELISA) were applied to detect AD-related pathology. Visual signals were markedly obstructed following surgery to induce cataracts, and these mice presented an increased cerebral amyloid-beta (Aβ) load, while no significant alterations in the levels of enzymes associated with Aβ metabolism were detected. In addition, compared with control mice, cataract model mice presented increased astrogliosis and microgliosis, along with elevated levels of proinflammatory factors. Moreover, cataract model mice presented more pronounced cognitive impairments than did control mice. Our study offers experimental confirmation that cataract considerably contributes to the pathogenesis of AD, thereby emphasizing the importance of visual signals in maintaining cognitive well-being.

The mammalian cochlea relies on outer and inner hair cells (OHCs/IHCs) for sound amplification and signal transmission. Rab3-interacting molecular binding protein 2 (RIMBP2), expressed in receptor cells and neurons at synaptic active zones, remains poorly characterized in hearing. We therefore generated a Rimbp2 knockout (KO) mouse model (Rimbp2^-/-), which exhibited severe hearing loss with elevated thresholds, prolonged latencies, and reduced amplitudes in auditory brainstem response Wave I. OHC loss via apoptosis was correlated with threshold elevation. In IHCs, patch-clamp recordings revealed reduced exocytosis, including a diminished readily-releasable pool, impaired sustained release, and blocked fast endocytosis. Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs. These findings demonstrated RIMBP2's essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.

Maintaining a stable body temperature is essential for survival. Multiple brain regions contribute to thermoregulation, but their specific characteristics and underlying neural mechanisms in the coordination of thermoregulation are not fully clarified. Here, we reveal the distinct roles of two preoptic subregions in warm defense in mice: the anterior ventromedial preoptic area (VMPO) and the ventral part of the lateral preoptic nucleus (vLPO). VMPO vesicular glutamate transporter 2​​ (Vglut2) neurons exhibited dramatic responses to rising temperatures, producing a marked decrease in core temperature by warm defense responses. In contrast, excitatory and inhibitory vLPO neurons responded gently to warm stimuli, exerting moderate effects on warm defense. Further postsynaptic tracing and caspase ablation identified distinct cell type-specific downstream targets in the dorsomedial hypothalamus (DMH) mediating these different warm defense responses. Taken together, our findings reveal distinct yet complementary pathways in the preoptic DMH network that enable both rapid and fine-tuned regulation of body temperature under elevated thermal conditions.

Vestibular hair cells (HCs) in the inner ear, crucial for balance and spatial orientation, are classified into type I and type II subtypes, but the mechanisms regulating their differentiation remain unclear. In this study, we examined the role of Pou4f3, an important transcription factor, in vestibular HC differentiation using Pou4f3^DTR/DTR (deficient) and Pou4f3^CreER/CreER (knockout) mouse models. In Pou4f3-deficient mice, the HC number decreased, and immature HCs failed to develop type I characteristics, indicating a developmental arrest. While type II HCs differentiated normally, Pou4f3 deficiency disrupted HC bundle formation and cell polarity. Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification. This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.

Psychiatric disorders have emerged as significant contributors to the global burden of disease in recent decades. The endocannabinoid system (ECS) influences a range of physiological and pathophysiological processes, including nociception, cognition, appetite, memory, and behavior, serving as a crucial mediator in psychiatric disorders. Imaging the ECS provides valuable insights into the pathophysiological mechanisms underlying psychiatric disorders and enhances clinical management strategies. As an advanced noninvasive molecular imaging modality, positron emission tomography (PET) enables the in vivo exploration of biological processes at the cellular and molecular levels. Recent advancements have led to the development of numerous PET tracers that target various components of the ECS, offering opportunities to visualize, characterize, and quantify ECS activity in psychiatric disorders in vivo. In this review, we summarize the existing PET tracers for ECS imaging and discuss their applications in diverse psychiatric conditions, including cannabis use disorder, alcohol use disorder, post-traumatic stress disorder, schizophrenia, and eating disorders.

Cisplatin is a widely-used chemotherapeutic agent, but its dose-limiting ototoxicity often results in irreversible hearing loss. The pathogenesis involves oxidative stress, apoptosis, DNA damage, and inflammatory responses, yet effective preventive strategies remain limited. Here, we demonstrate that magnesium hydride (MgH₂), a hydrogen-releasing compound, provides robust protection against cisplatin-induced hearing loss. Our results showed that MgH₂ protected auditory function and preserved cochlear hair cells in vivo. Furthermore, it significantly attenuated cisplatin-induced oxidative stress and apoptosis in cultured HEI-OC1 (House Ear Institute-Organ of Corti 1) cells and cochlear explants. Notably, MgH₂ suppressed NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated inflammatory cascades, thereby limiting downstream inflammatory damage. These findings revealed that MgH₂ alleviated cisplatin-induced hearing loss through integrated antioxidant, anti-inflammatory, and anti-apoptotic pathways, with NLRP3 identified as a critical regulatory molecule. Collectively, our study provides compelling evidence for MgH₂ as a potential therapeutic candidate for the prevention of cisplatin-induced hearing loss.