Neuroscience
-
Manganese (Mn) intoxication is associated with neurological dysfunctions collectively known as Parkinsonism or Manganism. Like in Parkinson's disease, Manganism is associated with motor disturbances, together with non-motor symptoms including cognitive and neuropsychiatric deficits. Although sleep dysfunctions are commonly reported among workers exposed to Mn, their underlying pathophysiology remains unknown. ⋯ Upon release from LD into DD, Mn-treated rats expressed a normal and stable free-running period of their rest-activity rhythm (23.92±0.07h in Mn group vs. 24.01±0.04h in control rats). However, their rest-activity rhythm remained highly fragmented and less stable. Our results provide the first evidence that chronic Mn intoxication leads to impairment of rest-activity rhythms in addition to the motor and non-motor disturbances reported in Manganism.
-
Xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. However, the mechanism underlying the neurotoxicity of para-xylene (PX) to the central nervous system (CNS) in vivo is less clear. Here, we exposed Xenopus laevis tadpoles to sub-lethal concentrations of PX during the critical period of brain development to determine the effects of PX on Xenopus development and visual behavior. ⋯ In particular, the increase in apoptotic cells in PX-treated brains was also inhibited by GA treatment. These effects indicate that epigenetic regulation plays a key role in PX-induced apoptosis and animal behavior. In an effort to characterize the neurotoxic effects of PX on brain development and behavior, these results suggest that the neurotoxicity of PX requires further evaluation regarding the safety of commercial and industrial uses.
-
Songbirds, like humans, learn vocalizations and their striatum recruits new neurons in adulthood. Injury in striatal vocal nucleus Area X, involved in song learning and production in songbirds, is followed by massive regeneration. The newborn neurons arise from the subventricular zone (SVZ) rich in dopamine D3 receptors (D3Rs). ⋯ Moreover, lesion alone prolonged the song duration and this may be facilitated by D3Rs in RA. Parallel lesion and stimulation of D3Rs prolonged it even more, while blocking of D3Rs abolished the lesion-induced effect. These data suggest that D3R stimulation after striatal injury accelerates the striatal recovery and can cause behavioral alterations.
-
Hindbrain dorsal vagal complex A2 noradrenergic signaling represses the pre-ovulatory luteinizing hormone (LH) surge in response to energy deficiency. Insulin-induced hypoglycemia augments A2 neuron adenosine 5'-monophosphate-activated protein kinase (AMPK) activity and estrogen receptor-beta (ERβ) expression, coincident with LH surge suppression. We hypothesized that ERβ is critical for hypoglycemia-associated patterns of LH secretion and norepinephrine (NE) activity in key reproduction-relevant forebrain structures. ⋯ Results provide novel evidence for ERβ-dependent caudal hindbrain regulation of LH and counter-regulatory hormone secretion during hypoglycemia. Observed inhibition of LH likely involves mechanisms at the axon terminal that impede GnRH neurotransmission. Data also show that caudal hindbrain ERβ exerts site-specific control of NE activity in forebrain projection sites during hypoglycemia, including the ARH where prepro-kisspeptin may be a target of that signaling.
-
Microglial cells are the pivotal immune cells of the central nervous system. Adult microglia cells under physiological conditions are in a ramification state with extensively branched processes. Upon disease stimulation, they retract their processes and become activated. ⋯ Mechanistic studies confirmed that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signal, extracellular signal-regulated kinase 1/2 (ERK1/2) or small RhoGTPase activation mediated the effect of CC on microglial shape change based on the following observations: (i) CC induced a significant activation of the small RhoGTPase Rac1 and Cdc42; (ii) CC promoted the phosphorylation of ERK1/2 and Akt; (iii) inhibition of Rac1, Cdc42, ERK1/2, or the PI3K-Akt signal abolished the effect of CC on microglial shape change. These signal mechanisms were also ascertained in primary microglia. Our results explore a potential agent that promotes microglial ramification, and provide an alternative explanation for the neuroprotective effects of CC in various disease models such as brain ischemia and subarachnoid hemorrhage.