Neonatal olfactory bulbectomy induces anxiety-related behavior and modifies dopaminergic receptor expression in post-pubertal rats.

Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs (OB) send projections to various CNS regions including the nucleus accumbens (NAcc) and caudate-putamen (CPu). Both the NAcc and CPu receive important dopaminergic input. Emerging evidence suggests that dopamine (DA) is related to anxiety-related behaviors. Therefore, we aimed to investigate the consequences of neonatal olfactory bulbectomy (nOBX) to anxiety-related behavior as assayed in the elevated plus maze (EPM) as well as the expression of dopaminergic receptors (D1-like, D2-like, and D3) in the NAcc and CPu at pre- and post-pubertal ages in the rat. The results show that nOBX increased the number of entries in the open arm of the EPM post-pubertally, suggesting an anxiolytic-related effect. nOBX increased the D2-like binding in the NAcc shell and D3 binding in the NAcc core pre-pubertally. At post-pubertal ages, the D3 binding was reduced at the olfactory tubercle and islands of Calleja in nOBX rats. Alterations in the DA receptor expression may be one mechanism responsible for the observed behavioral modifications in nOBX rats.

Losartan enhances cognitive and structural neuroplasticity impairments in spontaneously hypertensive rats.

Hypertension is a risk factor for vascular dementia, which is the second most prevalent type of dementia, just behind Alzheimer's disease. This highlights the brain vulnerability due to hypertension, which may increase with aging. Thus, studying how hypertension affects neural cells and behavior, as well as the effects of antihypertensives on these alterations, it's important to understand the hypertension consequences in the brain. The spontaneously hypertensive rat (SHR) has been useful for the study of hypertension alterations in diverse organs, including the brain. Thus, we studied the losartan effects on cognitive and structural neuroplasticity impairments in SHR of 10 months of age. In the first instance, we evaluated the losartan effects on exploratory behavior and novel object recognition test (NORT) in the SHR. Then, we assessed the density and morphology of dendritic spines of pyramidal neurons from the prefrontal cortex (PFC) layers 3 and 5, and CA1 of the dorsal Hp (dHp). Our results indicate that in SHR, losartan treatment (2 months, 15 mg/Kg/day) reduces high blood pressure to age-matched vehicle-treated Wistar-Kyoto (WKY) rat levels. Moreover, losartan improved long-term memory in SHR compared with age-matched vehicle-treated WKY rats, without affecting the locomotor and anxiety behaviors. The behavioral improvement of the SHR can be associated with the increase in the number of dendritic spines and the mushroom spine population in the PFC and the dHp. In conclusion, losartan enhances cognitive impairments by controlling the high blood pressure and improving neuroplasticity in animals with chronic hypertension.

Cerebrolysin ameliorates prefrontal cortex and hippocampus neural atrophy of spontaneous hypertensive rats with hyperglycemia.

Hyperglycemia of diabetes mellitus causes damage at the vascular level, which at the renal level represents diabetic nephropathy. In this pathology, there is arterial hypertension. In addition, several reports suggest that hyperglycemia and arterial hypertension affect interneuronal communication at the level of dendritic morphology. We studied these changes in an animal model with streptozotocin-induced diabetes mellitus in the spontaneous hypertensive (SH) rat. Recent reports from our laboratory have demonstrated that cerebrolysin (CBL), a preparation of neuropeptides with protective and repairing properties, reduces dendritic deterioration in both pathologies, in separate studies. In the present study, we evaluated the effect of CBL using the animal model with hyperglycemia and arterial hypertension and assessed the dendritic morphology using a Golgi-Cox staining procedure. Our results suggest that CBL ameliorated the reduction in the number of dendritic spines in the PFC and hippocampus caused by hyperglycemia in the SH rat. In addition, CBL also increased distal dendritic length in the PFC and hippocampus in hyperglycemic SH rats. Consequently, the CBL could be a therapeutic tool used to reduce the damage at the level of dendritic communication present in both pathologies.

Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1.

The animal model of streptozotocin-induced diabetes mellitus type 1 (DM1) is used to study neuronal and behavioral changes produced by an increase in blood-glucose levels. Our previous report showed that chronic streptozotocin administration induced atrophy of dendritic morphology of pyramidal neurons of the CA1 dorsal hippocampus. In addition, we showed that Cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in animal models of aging. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, after 6 weeks of hyperglycemia in mice (streptozotocin-induced DM1). The levels of glucose in the blood were evaluated before and after streptozotocin administration and only animals with more than 240 mg/dL of blood-levels of glucose were used. After streptozotocin treatment, the mice received 6 weeks of Cbl, locomotor activity was measured and dendritic morphological changes were evaluated using Golgi-Cox stain procedure, and analyzed by the Sholl method. In mice treated with streptozotocin there was a clear reduction in the dendritic length of pyramidal neurons of the CA1 and granular cells of the dental gyrus of the dorsal hippocampus. Interestingly, Cbl reversed the morphological changes induced by streptozotocin. Our results extend the list of abnormal morphological changes detected in this model of DM, and support the possibility that Cbl may have beneficial effects in the management of brain alterations induced by DM.

Subacute zinc administration and L-NAME caused an increase of NO, zinc, lipoperoxidation, and caspase-3 during a cerebral hypoxia-ischemia process in the rat.

Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc.

Expression and distribution of dopamine transporter in cardiac tissues of the guinea pig.

Dopamine transporter (DAT) is a membrane protein that it is a marker for dopaminergic neurons. In the present work, throught Western blot and autoradiographic studies with a selective ligand for DAT ([(3)H] WIN-35428) and noradrenaline transporter (NET) ([(3)H] Nisoxetine), we search the expression and distribution of DAT in comparison with NET, in cardiac tissue of guinea pig in order to support the presence of dopaminergic nerve cells into the heart. Expression of DAT, and NET were evidenced by a bands of 75 and 54 kDa, respectively in the heart. Binding for DAT and NET were found in the four cardiac chambers. However, DAT show heterogeneous distribution with binding in right atria and in both ventricles, whereas NET show homogenous distribution in the four cardiac chambers. The results show the expression of DAT in cardiac tissues with a different distribution compared with NET, being an evidence for the presence of dopaminergic nerve cells into the heart.

Dendritic morphology of neurons in medial prefrontal cortex, hippocampus, and nucleus accumbens in adult SH rats.

We have studied, in spontaneously hypertensive (SH) rats at different ages (2, 4, and 8 months old), the dendritic morphological changes of the pyramidal neurons of the medial prefrontal cortex (mPFC) and hippocampus and medium spiny neurons of the nucleus accumbens (NAcc) induced by the chronic effect of high-blood pressure. As control animals, we used Wistar-Kioto (WK) rats. Blood pressure was measured every 2 months to confirm the increase in arterial blood pressure. Spontaneous locomotor activity was assessed, and then brains were removed to study the dendritic morphology by the Golgi-Cox stain method followed by Sholl analysis. SH animals at 4 and 8 months of age showed decreased spine density in pyramidal neurons from the mPFC and in medium spiny cells from the NAcc. At 8 months of age as well the pyramidal neurons from the hippocampus exhibited a reduction in the number of dendritic spines. An increase in locomotion in a novel environment at all ages in the SH rats was observed. Our results indicate that high-blood pressure alters the neuronal dendrite morphology of the mPFC, hippocampus, and NAcc. The increased locomotion behavior supports the idea that dopaminergic transmission is altered in the SH rats. This could enhance our understanding of the consequences of chronic high-blood pressure on brain structure, which may implicate cognitive impairment in hypertensive patients.

Alteration in dendritic morphology of pyramidal neurons from the prefrontal cortex of rats with renovascular hypertension.

We have studied, in the rat, the dendritic morphological changes of the pyramidal neurons of the medial part of the prefrontal cortex induced by the chronic effect of high blood pressure. Renovascular hypertension was induced using a silver clip on the renal artery by surgery. The morphology of the pyramidal neurons from the medial part of the prefrontal cortex was investigated in these animals. The blood pressure was measured to confirm the increase in the arterial blood pressure. After 16 weeks of increase in the arterial blood pressure, the animals were sacrificed by overdoses of sodium pentobarbital and perfused intracardially with a 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain method and analyzed by the Sholl method. The dendritic morphology clearly showed that the hypertensive animals had an increase (32%) in the dendritic length of the pyramidal cells with a decrease (50%) in the density of dendritic spines when compared with sham animals. The branch-order analysis showed that the animals with hypertension exhibit more dendritic arborization at the level of the first to fourth branch order. This result suggests that renovascular hypertension may in part affect the dendritic morphology in this limbic structure, which may implicate cognitive impairment in hypertensive patients.

Efecto de la isquemia miocárdica aguda sobre el patrón del flujo venoso pulmonar: estudio experimental con ecocardiografía transesofágica / Effect of acute myocardial ischemia on the pattern of pulmonary venous flow

El análisis del flujo venoso pulmonar (FVP) con ecocardiografía Doppler se ha evaluado en diversas cardiopatías sin embargo, hasta el momento no se han publicado estudios enfocados a la isquemia miocárdica aguda. El propósito de este estudio es informar los cambios observados en el patrón normal del FVP por efecto de isquemia miocárdica en un modelo experimental. A 19 perros mestizos entre 18 y 25 Kg de peso, previa anéstesia con pentobarbital sódico intravenoso, se les practicó toracotomía y pericardiectomía con exposición del corazón. Con ecocardiografía transesofágica y Doppler pulsado se analizaron los flujos venoso pulmonar y mitral, con registros simultáneos de presiones intracavitarias de aurícula (AI) y ventrículo izquierdo (VI) antes y después de 30 minutos de oclusión parcial de la arteria coronaria descendente anterior en su tercio medio, después de la primera diagonal. Los parámetros estudiados incluyeron: velocidades máximas e integrales de los flujos anterógrados sistólicos (S) y diastólicos (D) del FVP, y del flujo de llenado rápido mitral (E), así como el tiempo de relajación isovolumétrica (TRIVI). Las presiones medidas en forma directa fueron: presión media de aurícula izquierda (PMAI), presión sistólica y distólica del VI. Con la isquemia miocárdica se observó una disminución en la velocidades pico e integral del FVP (S y D); velocidad S de 70.1ñ14.8 a 49.5ñ13.8 cm/seg (p<0.001) y D 41.1ñ16.5 a 29.5 ñ11.4 cm/seg (p=0.001). Asimismo hubo incremento en el TRIVI de 65.8ñ8.6 a 76ñ12.6 mseg (p<0.006) y de elevación de la presión media de AI (de 4.3ñ1 mmHg a 6.4ñ1.5 mmHg (p<0.001). Estos resultados sugieren que la isquemia miocárdica aguda altera el patrón normal del FVP, provocando una disminución significativa en las velocidades pico e integral de la fase sistólica y diastólica anterográda, así como un incremento en el TRIVI y de la PMAI. Tales hechos en conjunto pueden ser el reflejo de alteraciones de la función diastólica del VI