[HIV glycoprotein 120: possible etiological agent of AIDS-associated dementia].
The AIDS or HIV associated dementia is a cognitive-motor disease, characterized by a strong deficit of several cognitive processes such as attention, memory, sensory perception, motor control among others. The HIV associated dementia affects 30% of adult to 50% of infant HIV positive subjects. Since neurons are not infected by HIV, its principal target in the brain is microglia. The pathophysiology of this syndrome, therefore, remains to be disclosed. Several hypothesis have been proposed, one of them suggests that opportunistic infections can affect the brain. Another hypothesis suggests that microglia secretes toxic products as a result of HIV infection and those are the ones causing the damage and finally, the hypothesis, suggesting that the brain is damaged as a result of the insult caused by HIV-derived proteins. In vitro studies suggest that the HIVgp120, a viral surface protein, is highly neurotoxic. For example HIVgp120 increases cytoplasmic Ca+2 by two ways: facilitating glutamate neurotransmission increasing Ca+2 conductance, and activating the IP3 pathway, facilitating Ca+2 release from the smooth endoplasmic reticulum. This Ca+2 in turn, activates several internal signaling pathways such as the MAPK pathway. We use an animal model to test the HIVgp120 effect on neurophysiological signals and behavior as well as several pharmacological approaches to prevent the HIVgp120 neurotoxic effects. This review updates with the most recent literature discussing the potential mechanisms implicated in the pathophysiology of the AIDS dementia complex. We, in addition, hope the reader will be able to correlate the clinical symptoms observed in the HIV infected subjects and the HIVgp120-induced behavioral changes observed in animal models. Likewise, we discuss the new drugs we are testing, in order to offer a new pharmacological treatment to the patient.
Galicia
Oscar
O
Grupo de Neurociencias, Depto. de Fisiología, Fac. de Medicina, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.
Sánchez-Alavez
Manuel
M
Méndez Díaz
Mónica
M
Navarro
Luz
L
Prospero-García
Oscar
O
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D017088:AIDS-Related Opportunistic Infections / Q000150:complications; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D020013:Calcium Signaling; D016923:Cell Death; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D018913:Event-Related Potentials, P300; D018698:Glutamic Acid / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects* / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D020935:MAP Kinase Signaling System; D017628:Microglia / Q000473:pathology*; D017096:Prion Diseases / Q000473:pathology / Q000662:veterinary / Q000821:virology; D019707:Receptors, Chemokine / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology; D014779:Virus Replication
D019380:Anti-HIV Agents; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D018698:Glutamic Acid