Effects of hCG on reduced numbers of hCG receptors in the prefrontal cortex and cerebellum of rat models of Alzheimer's disease.

Age-associated changes in the levels of luteinizing hormone and human chorionic gonadotropin (hCG) are potential risk factors for Alzheimer's disease (AD); hCG concentration is related to the incidence of AD. The highest density of hCG receptors is in zones of the brain that are vulnerable to AD and streptozotocin (STZ) can decrease the density of this receptor. We investigated the effects of different doses of hCG on hCG receptor density in the prefrontal cortex and cerebellum in a rat model of STZ-induced AD. AD was induced by intracerebroventricular injection of 3 mg/kg STZ. The resulting AD rats were treated for 3 days with 50, 100 or 200 IU/200 µl hCG, or with saline as a control. Sections of prefrontal cortex and cerebellum were stained immunohistochemically and hCG receptor-immunoreactive (ir) neurons were counted. STZ injected into the lateral ventricles of rat brains reduced the density of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. hCG administration resulted in a significant dose-dependent increase in the number of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. The maximum increase in the number of receptors occurred following the 200 IU dose of hCG. Administration of hCG ameliorated the lowered density of hCG receptor-ir neurons in the cerebellum and prefrontal cortex in STZ-induced AD rats.

α2-Adrenoceptor-ir neurons' density changes after single dose of clonidine and yohimbine administration in the hippocampus of male rat.

OBJECTIVE: Despite the important role of α2-adrenoceptors in pain modulation processes, the impact of administration of α2-adrenoceptor agonist and antagonist on the density of hippocampal α2-adrenoceptor-immunoreactive neurons has not been investigated. Therefore, we aimed to determine the effect of single doses of clonidine and yohimbine on the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus. MATERIALS AND METHODS: Adult male Wistar rats received a single dose of clonidine (0.7 mg/kg) alone or 5 min after intraperitoneal (1 mg/kg) and/or intracerebroventricular (5 µg/kg) injection of yohimbine. After histological processing, neurons with α2-adrenoceptor immunoreactivity were identified and counted through immunohistochemical analysis of hippocampal regions. RESULTS: Clonidine slightly increased the number of α2-adrenoceptor-immunoreactive neurons in the hippocampal subregions compared with the normal saline group. Intraperitoneal injection of yohimbine followed by injection of clonidine significantly increased the number of α2-adrenoceptor-immunoreactive neurons in subregions cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3). Intracerebroventricular injection of yohimbine after injection of clonidine significantly reduced the number of α2-adrenoceptor-immunoreactive neurons in all hippocampal subregions. CONCLUSION: The present study demonstrates that intraperitoneal administration of α2-adrenoceptor agonist clonidine increases the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus, while intracerebroventricular injection of yohimbine decreases the density of these neurons.

Female rat hippocampal cell density after conditioned place preference.

The hippocampus is important for learning tasks, such as conditioned place preference (CPP), which is widely used as a model for studying the reinforcing effects of drugs with dependence liability. Long-term opiate use may produce maladaptive plasticity in the brain structures involved in learning and memory, such as the hippocampus. We investigated the phenomenon of conditioning with morphine on the cell density of female rat hippocampus. Forty-eight female Wistar rats weighing on average 200-250 g were used. Rats were distributed into eight groups. Experimental groups received morphine daily (three days) at different doses (2.5, 5, 7.5 mg/kg) and the control-saline group received normal saline (1 ml/kg), and then the CPP test was performed. Three sham groups received only different doses (2.5, 5, 7.5 mg/kg) of morphine without CPP test. Forty-eight hours after behavioural testing animals were decapitated under chloroform anaesthesia and their brains were fixed, and after tissue processing, slices were stained with cresyl violet for neurons and phosphotungstic acid haematoxylin for astrocytes. The maximum response was obtained with 5 mg/kg of morphine. The density of neurons in CA1 and CA3 areas of hippocampus after injection of morphine and CPP was decreased. The number of astrocytes in different areas of hippocampus was increased after injection of morphine and CPP. It seems that the effective dose was 5 mg/kg, as it led to the CPP. We concluded that both injection of mor phine and CPP can decrease the density of neurons and also increase the number of astrocytes in the rat hippocampus.

Scopolamine reduces the density of M1 muscarinic neurons in rats' hippocampus / La escopolamina reduce la densidad de las neuronas muscarínicas M1 en el hipocampo de ratas

Cholinergic system in CNS is involved in learning and memory. Scopolamine as muscarinic acetylcholine receptor antagonist is used for creation of memory impairment. The purpose of this study is evaluation of scopolamine-based amnesia on memory retention and the effect of this phenomenon on the number of neurons contains M1-receptors in the male Wistar rats hippocampal regions. Thirty-five male Wistar rats (200+/-20 g) were distributed randomly into five groups. Control group (intact samples) and 3 experimental groups with sham group (saline) were tested by the method of passive avoidance (shuttle box) in doses of 0.2, 0.5 and 1 mg/kg (intraperitoneally) as a single dose. After one week, memory test was taken from the rats. Finally, brains dissected from sacrificed rats, and then processed tissues were stained with antibody against M1 receptors (Immunohistochemistry technique) followed by counting of hippocampal CA1, CA3 and DG regions. Our results showed significant decrease in neurons contains M1-receptors in all area of hippocampus. We found that the less number of M1-neurons showed in 1 mg/kg dose of scopolamine. We concluded that scopolamine as muscarinic acetylcholine receptor antagonist can reduce dose-dependently the density of M1-neurons in all areas of hippocampus.

El sistema colinérgico en el SNC está implicado en el aprendizaje y la memoria. La escopolamina como receptor antagonista de acetilcolina muscarínico es utilizada para la creación del deterioro de la memoria. El propósito de este estudio es la evaluación de la amnesia basada en escopolamina sobre la retención de memoria y el efecto de este fenómeno en la cantidad de neuronas en receptores M1 en regiones del hipocampo en ratas macho Wistar. Se distribuyeron al azar, 35 ratas macho Wistar (200+/-20 g) en cinco grupos. El grupo de control (muestras intactas) y 3 grupos experimentales con grupo de tratamiento simulado (solución salina) analizadas por método de evasión pasiva (caja de transporte) en dosis de 0,2; 0,5 y 1 mg/kg (por vía intraperitoneal) como dosis única. Al término de una semana se realizó prueba de memoria de las ratas. Por último, los cerebros diseccionados de las ratas sacrificadas y los tejidos procesados fueron teñidos con anticuerpos contra los receptores M1 (técnica inmunohistoquímica), seguido por el recuento de regiones CA1, CA3 y DG del hipocampo. Nuestros resultados mostraron una disminución significativa en las neuronas con receptores M1 en toda el área del hipocampo. Se encontró que el número menor de neuronas M1, y fue demostrado en 1 mg/kg de dosis de escopolamina. Llegamos a la conclusión de que la escopolamina como antagonista del receptor de acetilcolina muscarínico puede, dependiendo de la dosis, reducir la densidad de neuronas M1 en todas las áreas del hipocampo.

Effect of Gingko biloba extract on scopolamine-induced apoptosis in the hippocampus of rats.

Apoptosis, known as programmed cell death, plays a crucial role in normal development and tissue homeostasis. Apoptosis is also involved in neurodegenerative diseases such as Alzheimer's disease. Amnesia refers to the loss of memory and can also be a warning sign of neurodegenerative diseases. The antioxidant properties of Ginkgo biloba extract was known previously. Therefore, the aim of this study was to examine the effects of Ginkgo biloba extract on the rat's hippocampal apoptotic neurons number after Scopolamine based amnesia. Thirty-six adult male Wistar rats were used. Rats were randomly divided into control, sham, protective and treatment groups. The rats in the sham group received only scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received Ginkgo biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before/after scopolamine injection. Then 48 h after the last injection, the brains of rats were withdrawn and fixed with paraformaldehyde, and then, after histological processing, the slices were stained with the TUNEL kit for apoptotic neurons. Data were compared by the ANOVA Post Hoc Tukey test; P < 0.05 was considered significant. Our results showed that Scopolamine (in the sham group) increased significantly the number of apoptotic neurons in all areas of the hippocampus compared with the control. Whereas, Ginkgo biloba extract reduce the neuronal apoptosis in the hippocampus before and/or after encounter with scopolamine. We concluded that pretreatment and treatment injection of Ginkgo biloba extract can have a protective effect for neurons and it can limit apoptosis in all area of the hippocampus.