Neuroscience
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Patients with schizophrenia present with various symptoms related to different domains. Abnormalities of auditory and visual perception are parts of a more general problem. Nevertheless, the relationship between the lifetime history of auditory verbal hallucination (AVH), one of the most prevalent symptoms in schizophrenia, and visuospatial deficits remains unclear. ⋯ The amplitude of P3b, a cognitive evaluation component, was also decreased in schizophrenia. Compared to AVH and HC groups, the patients in the NH group had altered microstate patterns: P3b was replaced by a novelty component, P3a. Although the difference between both patient groups was only based on the presence of AVHs, our findings indicated that patients had specific visuospatial deficits associated with a lifetime history of hallucinations: patients with AVHs showed early visual component alterations in the right hemisphere, and those without AVHs had more prominent visuospatial impairment.
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Deficiency in peroxisome proliferator-activated receptor gamma coactivator 1-alpha. (PGC-1α) expression or function is implicated in numerous neurological and psychiatric disorders. PGC-1α is required for the expression of genes involved in synchronous neurotransmitter release, axonal integrity, and metabolism, especially in parvalbumin-positive interneurons. As a transcriptional coactivator, PGC-1α requires transcription factors to specify cell-type-specific gene programs; while much is known about these factors in peripheral tissues, it is unclear if PGC-1α utilizes these same factors in neurons. ⋯ In ERRα null mice, PGC-1α-dependent genes were reduced in multiple regions, including neocortex, hippocampus, and cerebellum, though not to the extent observed in PGC-1α null mice. Behavioral assessment revealed ambulatory hyperactivity in response to amphetamine and impairments in sensorimotor gating without the overt motor impairment characteristic of PGC-1α null mice. These data suggest that ERRα is required for normal levels of expression of PGC-1α-dependent genes in neurons but that additional factors may be involved in their regulation.
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MiR-186-5p dysregulation leads to depression-like behavior by de-repressing SERPINF1 in hippocampus.
Diagnosis of major depressive disorder (MDD) is perplexing due to its multifactorial etiologies. Here, we isolated exosomes from the peripheral blood of MDD patients and healthy control subjects for mass spectrometry-based label-free quantitative proteomics. We identified that SERPINF1 is significantly diminished in the peripheral blood-derived exosomes of MDD patients compared to the healthy control subjects. ⋯ Inhibiting the microRNA significantly restores the hippocampal SERPINF1 mRNA and protein expression, and ameliorates the depressive-like behaviors including sucrose preference and extended immobility time in the forced swim test. Instead, overexpressing miR-186-5p through tail intravenous injection of the mimics molecularly and behaviorally phenocopies the CUMS mice in wild-type mice. Our results indicate that the exosomal SERPINF1 in peripheral blood could serve as a reliable biomarker indicating MDD development, and miR-186-5p is a potential therapeutic target for the disease.
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Pain is the major non-motor symptom in Parkinson's disease (PD). Preclinical studies have mostly investigated mechanical pain by considering the decrease in a nociceptive threshold. Only a few studies have focused on thermal pain in animal models of PD. ⋯ In 6-OHDA-lesioned rats, there was a significant augmentation in the expression of both protein kinase C gamma (PKCγ) and glutamate decarboxylase 67 (GAD67) in the SDH. This highlighted an increase in excitation and a decrease in inhibition in the SDH. Overall, the present study demonstrated a clear cold thermal hypersensitivity, in addition to a mechanical one, in 6-OHDA-lesioned rats.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) binds to PACAP-specific (PAC1) receptors in multiple hypothalamic areas, especially those regulating energy balance. PACAP neurons in the ventromedial nucleus (VMN) exert anorexigenic effects within the homeostatic energy balance circuitry. Since PACAP can also reduce the consumption of palatable food, we tested the hypothesis that VMN PACAP neurons project to the ventral tegmental area (VTA) to inhibit A10 dopamine neurons via PAC1 receptors and KATP channels, and thereby suppress binge-like consumption. ⋯ This response was again completely blocked by tolbutamide and PACAP6-38, and associated with a hyperpolarization and decrease in firing. These findings demonstrate that PACAP activates PAC1 receptors and KATP channels to inhibit A10 dopamine neurons and sex-dependently suppress binge-like consumption. Accordingly, they advance our understanding of how PACAP regulates energy homeostasis via the hedonic energy balance circuitry.