Hypothalamus Of Young Rats Research Articles

Stereotaxic surgery for implantation of guide cannulas for microinjection into the dorsomedial hypothalamus in young rats

Stereotaxic surgery to implant guide cannulas into the rodent brain is a frequently used technique to deliver drugs to targeted brain regions in awake, freely moving animals. There are limited reports, however, of central injections in young animals, and no information on cannula implantation for drug administration into the dorsomedial hypothalamus (DMH) in young rats. Our protocol describes a simple and successful method for implanting guide cannulas in the brains of young, male Sprague-Dawley rats and outlines newly developed stereotaxic coordinates to accurately target the dorsomedial hypothalamus.•Stereotaxic surgical procedure for guide cannula implantation in the DMH in young rats.•Development of stereotaxic coordinates of the DMH in young rats.•Microinjection of drugs into the young rat brain.

Acute Exposure of the Mediobasal Hypothalamus to Amyloid-β25-35 Perturbs Hepatic Glucose Metabolism.

Patients with Alzheimer's disease (AD) have a higher risk for developing insulin resistance and diabetes. Amyloid plaques, a hallmark of AD, are composed of amyloid-β (Aβ). Because the mediobasal hypothalamus controls hepatic glucose production, we examined the hypothesis that its exposure to Aβ perturbs the regulation of glucose metabolism. The infusion of Aβ25-35, but not its scrambled counterpart, into the mediobasal hypothalamus of young rats, increased circulating glucose as a consequence of enhanced hepatic glucose production during pancreatic clamp studies. These findings suggest a link between AD and alterations of glucose metabolism.

Aging-related changes of microglia and astrocytes in hypothalamus after intraperitoneal injection of hypertonic saline in rats

To examine the aging-related changes of microglia and astrocytes in hypothalamus of rats after intraperitoneal injection of hypertonic saline in rats, old- and young-aged rats were injected with hypertonic saline solution into peritoneal cavity. Lectin histochemical techniques using Ricinus communis agglutinin-1 (RCA-1) and immunocytochemical method employing antibody against glial fibrillary acidic protein (GFAP) were used to demonstrate microglia and astrocytes in the hypothalamus of the rats, and the positively-stained cells were analyzed by computer-assisted image analysis system. Our results showed that the numbers of microglia and astrocytes were significantly increased in the hypothalamus of old-aged rats. After intraperitoneal injection of hypertonic saline, the number of microglia was significantly decreased in the hypothalamus of both young- and old-aged groups. After introperitoneal injection of hypertonic saline, the number of GFAP positive cells was significantly increased in the hypothalamus of young rats, but the number of GFAP positive cells did not show significant change in the hypothalamus of old rats. It is concluded that in the hypothalamus of old-aged rats, the increase of microglia may be related with the aging or degeneration of neurons, and the increase of astrocytes may provide more nourishment required by the aged neurons. The microglia and astrocytes in the hypothalamus of the two group rats may be affected by hypertonic saline, and the response of these cells to the stimuli is characterized by some aging-related changes.

In Vitro Effects of Polychlorinated Biphenyls and Hydroxy Metabolites on Nitric Oxide Synthases in Rat Brain

Nitric oxide synthases (NOS) play a key role in motor activity in the cerebellum, hormonal regulation in the hypothalamus, and long-term potentiation (LTP), learning, and memory processes in the hippocampus. Developmental exposure to polychlorinated biphenyls (PCBs) has been shown to affect psychomotor functions, learning and memory processes, and to inhibit LTP. We hypothesized that PCBs may disrupt the regulation of such neurological functions by altering NOSs. We have studied the in vitro effects of several PCB congeners and some hydroxy PCBs on NOS activity in cytosolic (presumably neuronal NOS [nNOS]) and membrane (presumably endothelial NOS [eNOS]) fractions in different brain regions of young and adult rats. Among the two selected dichloro PCBs, the ortho-PCB, 2,2′-dichlorobiphenyl (DCB), inhibited both cytosolic and membrane NOS activity at low micromolar concentrations (3–10 μM) in the selected brain regions of all age groups while the non-ortho-PCB, 4,4′-DCB, did not. 2,2′-DCB inhibited cytosolic NOS to a greater extent than membrane NOS. Pentachloro-PCBs (PeCBs) and hexachloro-PCBs (HCBs) did not have a significant effect on adult cerebellar cytosolic or membrane NOS. However, mono- and dihydroxy derivatives of HCBs significantly decreased cytosolic NOS (IC50s: 16.33 ± 0.47 and 33.65 ± 4.33 μM, respectively) but resulted in a marginal effect on membrane NOS in the cerebellum. Among three adult rat brain regions, the hypothalamic cytosolic NOS was the most sensitive to 2,2′-DCB. Also, cytosolic NOS in the cerebellum and hypothalamus of young rats was less sensitive than in the older rats. In summary, these results indicate that only di-ortho-PCB inhibited both NOS and hydroxy substitution of one or more chlorine molecules significantly increased the potency of both ortho- and non-ortho-HCBs. The selective sensitivity of NOS to dichloro- ortho-PCB and hydroxy metabolites suggests that the inhibition of NOS could play a role in the neuroendocrine effects as well as learning and memory deficits caused by exposure to PCBs.

Impaired leptin signal transduction with age-related obesity

Leptin contributes to the regulation of both food intake and energy expenditure. We previously demonstrated that the F-344×BN rat, a rodent model for late-onset obesity, is leptin resistant, suggesting that leptin signal transduction may be impaired in these aged, overweight rats. To test this hypothesis, we examined the in vivo dose–response and time–course response of leptin-induced STAT3 activation (phosphorylation and binding activity to the SIE M67 oligonucleotide) in the hypothalamus of young rats along with the dose–response leptin-induced STAT3 phosphorylation (P-STAT3) and maximum increase in binding activity in young and aged rats. In young rats there was a dose (0–1 mg, iv) and time dependent increase in P-STAT3 and in P-STAT3 binding activity. P-STAT3 paralleled the rise and fall in serum leptin levels with P-STAT3 elevated for at least 4 h with return to basal levels by 14 h after 1 mg leptin. The maximum level of leptin-induced P-STAT3 was unchanged with age, but the dose for half maximal phosphorylation was greater in aged (138 μg) compared with young (26 μg) rats. In addition, the leptin-induced increase in P-STAT3 transcription factor binding was diminished in aged rats. These data suggest that leptin signal transduction, in vivo, demonstrate a time and dose response increase paralleling the rise and fall in serum leptin, suggesting that serum leptin levels are the most important factor in determining leptin-induced phosphorylation of STAT3 in the hypothalamus. In addition, aged, overweight rats demonstrate reduced signal transduction in response to leptin, with reduced sensitivity for STAT3 phosphorylation and diminished leptin-induced P-STAT3 transcription factor binding. This impaired leptin signal transduction may be due to either the elevated obesity with age or due to age itself or both.

Rat Gonadotropin Release Stimulated <i>in vitro</i> by GnRH-Depleted Rat Brain Extracts

A study was made to compare the LH and FSH release patterns from isolated adult rat pituitaries in response to exposure to acidic extracts of rat hypothalamus or brain or to acidic extracts of GnRH-depleted hypothalamus, cerebral cortex, or cerebellum of adult (90-100 days old) or young (14 days old) rats of both sexes, using a continuous perifusion system. Hypothalami of adult rats contained 3-5 ng of radioimmunoreactive GnRH, while the corresponding cerebral cortex and cerebellum contained none, or extremely low levels of GnRH. Adult hypothalamic extract (HE) stimulated considerably greater LH and FSH release than was induced by cortical extract (CE) or cerebellar extract (CBE). Removal of assayable GnRH from HE by incubation with anti-GnRH serum reduced, but did not eliminate, release of both LH and FSH, suggesting that GnRH is the principal but not sole agent responsible for both LH and FSH secretions. Adult male HE released slightly more LH and FSH than did female HE due to its greater GnRH content. GnRH-depleted CE or CBE from both sexes induced LH and FSH releases qualitatively and quantitatively similar to those induced by CE, CBE or GnRH-depleted HE. Untreated extracts or GnRH-depleted extracts of all three brain regions from 14-day-old rats of both sexes induced similar LH and FSH releases as those of adult CE or CBE. Hypothalamus of young rats, which contained about 0.5 ng of immunoassayable GnRH did not release more LH and FSH than the corresponding cortex or cerebellum did. The data indicate that all brain regions so far studied, regardless of sex or age, contained presumably nonspecific substance(s), other than GnRH, capable of stimulating minor but significant LH and FSH releases. Their nature or role in physiological regulation of gonadotropin secretion is unknown, but must be considered, since current concepts, in which GnRH is the sole hypothalamic gonadotropin regulator, are not adequate.

Failure to demonstrate uptake of 3H-testosterone by the hypothalamus of young rats.

Failure to demonstrate uptake of 3H-testosterone by the hypothalamus of young rats.