Neuroscience
-
The cuneiform (CnF) and Kolliker-Fuse (KF) nuclei are implicated in several functions including regulation of cardiovascular system and pain modulation. The KF also is a potential candidate for relaying the CnF cardiovascular responses to the rostral ventrolateral medulla (RVLM). In a previous study we showed that blockade of the KF strongly attenuated the short responses and moderately attenuated the long responses to glutamate microinjection into the CnF, suggesting that the cardiovascular effects of the CnF, especially the short responses, were mediated by the KF. ⋯ In about one fourth of the cases there were no responses to stimulation. Various patterns of each group were presented and compared between cardiovascular and single unit responses. Similarities were found between cardiovascular and single unit response patterns, suggesting a significant role of KF neurons in mediating the CnF cardiovascular responses to the RVLM.
-
Alzheimer's disease (AD) is the most prevalent form of dementia affecting the elderly. Evidence has emerged signifying that stimulation of the reelin pathway should promote neural plasticity and suppress molecular changes associated with AD, suggesting a potential therapeutic application to the disease. ⋯ F-spondin overexpression also suppressed endogenous levels of amyloid beta (Aβ(42)) in these mice and reduced Aβ plaque deposition while improving synaptophysin expression in transgenic mouse models of AD. These data demonstrate pathologic and cognitive improvements in mice through F-spondin overexpression.
-
Melanin-concentrating hormone (MCH) is synthesized by neurons located in the hypothalamus and projecting to widespread regions of the brain, including the locus coeruleus (LC), through which MCH could modulate sleep-wake states. Yet MCH does not appear to exert direct postsynaptic effects on target neurons, including the noradrenergic LC neurons. Previous studies using in situ hybridization showed that MCH neurons synthesize glutamic acid decarboxylase (GAD) and could thus utilize GABA as a neurotransmitter. ⋯ Moreover, of the MCH varicosities, ∼5% abutted puncta that were immunostained for gephyrin, the postsynaptic marker for GABAergic synapses. In triple-immunostained sections viewed with confocal laser scanning microscopy, we established that MCH varicosities that also contained VGAT or abutted upon gephyrin puncta contacted the tyrosine hydroxylase-immunostained neurons of the LC. Our results suggest that although MCH neurons can influence noradrenergic LC neurons through paracrine release and indirect effects of their peptide, they can also do so through synaptic release and direct postsynaptic effects of GABA and thus serve to inhibit the LC neurons during sleep, when they are silent, and the MCH neurons discharge.
-
Since homocysteine (Hcy) is considered a risk factor to cerebral diseases and adenine nucleotides are important molecules to brain normal function, in the present study we investigated the effect of chronic mild hyperhomocysteinemia on ectonucleotidase activities and expression in rat cerebral cortex. The levels of ATP, ADP, AMP and adenosine (Ado) in cerebrospinal fluid (CSF) of adult rats also were evaluated by high-performance liquid chromatography. For the chronic chemically induced mild hyperhomocysteinemia, Hcy (0.03 μmol/g of body weight) was administered subcutaneously from the 30th to the 60th day of life. ⋯ Results showed that Hcy significantly decreased nucleotide hydrolysis in the synaptosomal fraction and increased E-NTPDase1 and ecto-5'-nucleotidase transcripts in rat cerebral cortex. ATP levels were significantly increased, while Ado decreased in CSF of Hcy-treated rats. These findings suggest that the unbalance in ATP and Ado levels may be, at last in part, involved in the cerebral toxicity of mild hyperhomocysteinemia.
-
Recent studies highlight that the brain glutamate system is involved in the etiology of depression and glutamatergic-targeting drugs are currently being explored as novel antidepressant medications. Previous studies reveal that the selective metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) produces antidepressant-like effects in behavioral despair and olfactory bulbectomy models. The current study aimed to further explore its behavioral actions in additional animal models of depression (forced swimming test (FST) and learned helplessness (LH) test) and its underlying neurobiological mechanisms. ⋯ Sub-chronic, five-day treatment of MPEP (30 mg/kg) decreased escape failures in animals that had developed LH symptoms. This sub-chronic treatment also increased hippocampal brain-derived neurotrophic factor (BDNF) protein levels in both non-stressed and stressed animals and restored the stress-induced down-regulation of BDNF expression. Current findings provide strong evidence for further studies of MPEP as a tool to explore novel antidepressants.