Neuroscience
-
Carotid artery stenosis appears to be an independent risk factor for cognitive impairment. But the mechanisms of cognitive impairments occurring in patients with asymptomatic carotid stenosis are poorly understood. One important reason is the absence of a good carotid stenosis model. ⋯ Moderate carotid stenosis rats had a partial cognitive impairment, but there were no changes in ACh level and morphological damage in hippocampus. Meanwhile, mild carotid stenosis rats had no cognitive impairment compared to sham-operated rats. The results of this study suggest that different degrees of carotid stenosis induce different cognitive changes in aged rats.
-
The clustered protocadherin genes encode a diverse collection of neuronal cell surface receptors. These genes have been proposed to play roles in axon targeting, synaptic development and neuronal survival, although their specific cellular roles remain poorly defined. In zebrafish there are four clustered protocadherin genes, two pcdhα clusters and two pcdhγ clusters, that give rise to over 100 distinct proteins, each with a distinct ectodomain (EC). ⋯ Consistent with studies in mouse, we find that Pcdhα and Pcdhγ are present in a complex, as they can be co-immunoprecipitated from zebrafish larval extracts. This interaction is direct and occurs through the ECs of these proteins. Using standard bead aggregation assays, we find no evidence for intrinsic adhesive ability by either Pcdhγ or Pcdhα, suggesting that they do not function as cell adhesion molecules.
-
Exploration of the molecular dynamics underlying regeneration in the central nervous system of regeneration-competent organisms has received little attention thus far. By combining a cerebellar lesion paradigm with differential proteome analysis at a post-lesion survival time of 30 min, we screened for protein candidates involved in the early stages of regeneration in the cerebellum of such an organism, the teleost fish Apteronotus leptorhynchus. Out of 769 protein spots, the intensity of 26 spots was significantly increased by a factor of at least 1.5 in the lesioned hemisphere, relative to the intact hemisphere. ⋯ Proteins whose abundance was significantly increased include: erythrocyte membrane protein 4.1N, fibrinogen gamma polypeptide, fructose-biphosphate aldolase C, alpha-internexin neuronal intermediate filament protein, major histocompatibility complex class I heavy chain, 26S proteasome non-ATPase regulatory subunit 8, tubulin alpha-1C chain, and ubiquitin-specific protease 5. Proteins with significantly decreased levels of abundance include: brain glycogen phosphorylase, neuron-specific calcium-binding protein hippocalcin, and spectrin alpha 2. We hypothesize that these proteins are involved in energy metabolism, blood clotting, electron transfer in oxidative reactions, cytoskeleton degradation, apoptotic cell death, synaptic plasticity, axonal regeneration, and promotion of mitotic activity.
-
Multiple sclerosis (MS) is characterized by inflammatory process associated with nitric oxide (NO) and the related species production in CNS, which can nitrosylate protein thiols and modulate their structure and functions, also reducing the CNS content of redox active compounds, such as glutathione (GSH). We have evaluated the relationships between S-nitrosothiols (RSNO) and GSH in the experimental model of MS - experimental autoimmune encephalomyelitis (EAE), during the treatment with inducible NO synthase inhibitor - aminoguanidine (AG) and thiol donor molecule - N-acetyl-L-cysteine (NAC). ⋯ The findings of our work suggest a potential role of RSNO and GSH in early clinical presentation of experimental MS, that might be also useful as predictive parameters for MS treatment directed to increased GSH and thiol pool in CNS.
-
It is well known that the preoptic-anterior hypothalamus (PO/AH), containing temperature-sensitive and -insensitive neurons plays an important role in precise thermoregulatory responses. Previous in vivo studies suggest that the arginine vasopressin (AVP) is an important endogenous mediator in thermoregulation, since AVP and V(1a) vasopressin receptor antagonist can induce hypothermia and hyperthermia, respectively. In the present study, intracellular electrophysiological activity was recorded from temperature-sensitive and -insensitive neurons in rat PO/AH tissue slices, using a whole-cell patch clamp. ⋯ V(1a) vasopressin receptor participated in these responses. Since excited warm-sensitive neurons or inhibited cold-sensitive and temperature-insensitive neurons promote heat loss or suppress heat production and retention. These results that AVP excites warm-sensitive neurons and inhibits cold-sensitive and temperature-insensitive neurons suggest a probable mechanism of AVP-induced hypothermia.