0000000000010478
AUTHOR
Vicente Hernandez-rabaza
Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications
The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG) of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurog…
Enhanced habit-based learning and decreased neurogenesis in the adult hippocampus in a murine model of chronic social stress
Abstract Stress can induce preferential engagement of habit learning mediated by the basal ganglia, relative to learning that involves complex spatial associations contributed by the hippocampal formation. We explored in mice the influence that chronic episodes of social stress exert on the selection of cognitive/spatial vs. habit-based learning strategies. Male mice were exposed to repeated episodes of social confrontation and were categorized as dominant, subordinate or undetermined according to quantitative ethologically relevant parameters of aggression. Mice were then trained in a conditional discrimination task in the T-maze in the presence of allocentric cues until five correct choic…
Sildenafil reduces neuroinflammation and restores spatial learning in rats with hepatic encephalopathy: underlying mechanisms
Background: There are no specific treatments for the neurological alterations of cirrhotic patients with minimal hepatic encephalopathy (MHE). Rats with MHE due to portacaval shunt (PCS) show impaired spatial learning. The underlying mechanisms remain unknown. The aims of this work were to assess: (a) whether PCS rats show neuroinflammation in hippocampus, (b) whether treatment with sildenafil reduces neuroinflammation and restores spatial learning in PCS rats, and (c) analyze the underlying mechanisms. Methods: Neuroinflammation was assessed by determining inflammatory markers by Western blot. Phosphorylation of MAP-kinase p38 was assessed by immunohistochemistry. Membrane expression of GA…
Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.
The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neur…
Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy
Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced n…
Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal.
Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expressio…
Modulation of GABAA receptors by neurosteroids. A new concept to improve cognitive and motor alterations in hepatic encephalopathy
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome affecting patients with liver diseases, mainly those with liver cirrhosis. The mildest form of HE is minimal HE (MHE), with mild cognitive impairment, attention deficit, psychomotor slowing and impaired visuo-motor and bimanual coordination. MHE may progress to clinical HE with worsening of the neurological alterations which may lead to reduced consciousness and, in the worse cases, may progress to coma and death. HE affects several million people in the world and is a serious health, social and economic problem. There are no specific treatments for the neurological alterations in HE. The mechanisms underlying the cognitive …
P1296 : Blocking NMDA receptors prolongs survival in rats with acute liver failure by dual protective mechanisms in kidney and brain
were 1094.67±239.37mIU/ml. The difference in values between these groups was statistically significant (p = 0.004). There was a statistically significant difference in total leucocyte count, serum creatinine, INR and cleaved CK18 M30 levels among those that survived vs expired. Multivariate analysis found that all these independently predict mortality. A receiver operating characteristic curve was drawn for the new score. The score found was compared with the King’s College criteria and the MELD score, the new scoring system was found to have higher sensitivity and specificity for mortality compared with other standard prognostic markers in ALF, and has a better diagnostic accuracy (Table 1…