Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole

Cognition is a group of mental processes that includes the capacity to perceive, think, learn and to study, and the capacity of the brain to analyze information and program adaptive behaviour. Although there has been an appreciable evolution in the therapy of psychoses in the last twenty-five years, cognitive disturbances still persist in spite of antipsychotic treatment. The cognitive decay disrupts the ability of clinically diagnosed patients with psychoses, mainly schizophrenia, to learn and to memorize skills that are useful for their family and social relationships. Moreover, cognitive deficiency is often considered to be crucial for further rehabilitation. In atypical antipsychotics there are big differences in the effects on cognitive functions. Some clinical studies demonstrate the benefits of a third generation of antipsychotics on cognitive functions in patients treated for mental illnesses. In the present study we have reviewed many articles investigating the influence of aripiprazole on cognition in human and animal subjects. Aripiprazole is a third generation antipsychotic drug that possesses a unique pharmacodynamic profile, which in conjunction with recently published scientific data on the drugs’ influence on antidepressant, anxiolytic and cognitive functions, suggests a highly positive future potential for restorative cognitive treatment and ongoing healthy function. The data included in the review will contribute to determining the potential benefits of aripiprazole on memory and training processes

Rac1b increases with progressive tau pathology within cholinergic nucleus basalis neurons in alzheimer\u27s disease

Cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons display neurofibrillary tangles (NFTs) during Alzheimer\u27s disease (AD) progression, yet the mechanisms underlying this selective vulnerability are currently unclear. Rac1, a member of the Rho family of GTPases, may interact with the proapoptotic pan-neurotrophin receptor p75 NTR to induce neuronal cytoskeletal abnormalities in AD NB neurons. Herein, we examined the expression of Rac1b, a constitutively active splice variant of Rac1, in NB cholinergic neurons during AD progression. CBF tissues harvested from people who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment, or AD were immunolabeled for both p75 NTR and Rac1b. Rac1b appeared as cytoplasmic diffuse granules, loosely aggregated filaments, or compact spheres in p75 NTR-positive NB neurons. Although Rac1b colocalized with tau cytoskeletal markers, the percentage of p75 NTR-immunoreactive neurons expressing Rac1b was significantly increased only in AD compared with both mild cognitive impairment and NCI. Furthermore, single-cell gene expression profiling with custom-designed microarrays showed down-regulation of caveolin 2, GNB4, and lipase A in AD Rac1b-positive/p75 NTR-labeled NB neurons compared with Rac1b-negative/p75 NTR-positive perikarya in NCI. These proteins are involved in Rac1 pathway/cell cycle progression and lipid metabolism. These data suggest that Rac1b expression acts as a modulator or transducer of various signaling pathways that lead to NFT formation and membrane dysfunction in a subgroup of CBF NB neurons in AD. © 2012 American Society for Investigative Pathology