RESUMEN
Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5g/kg ethanol (two doses, two hours apart) on PD 5, 7, and 9. On PD 35, animals received a running wheel or remained sedentary for 48days before behavioral testing and perfusion on PD 83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.
Asunto(s)
Depresores del Sistema Nervioso Central/toxicidad , Etanol/toxicidad , Interneuronas/efectos de los fármacos , Discapacidades para el Aprendizaje , Parvalbúminas/metabolismo , Condicionamiento Físico Animal , Corteza Prefrontal/efectos de los fármacos , Factores de Edad , Animales , Animales Recién Nacidos , Reacción de Prevención/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Recuento de Células , Interneuronas/metabolismo , Discapacidades para el Aprendizaje/inducido químicamente , Discapacidades para el Aprendizaje/patología , Discapacidades para el Aprendizaje/rehabilitación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Nestina/genética , Nestina/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Corteza Prefrontal/patología , Trastornos Psicomotores/etiologíaRESUMEN
The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.