Biomedical subjects

Jennifer L Bennett

Publications and source records attributed to Jennifer L Bennett.

4 recordsLinked to original sources

PubMed2006

Intraventricular insulin and leptin decrease sucrose self-administration in rats.

Data from our laboratory and others have demonstrated an effect of the candidate adiposity signals insulin and leptin to decrease brain reward function, as assessed by lateral hypothalamic self-stimulation and food-conditioned place preference. In this study, we evaluated the effect of centrally administrated insulin or leptin to acutely decrease motivated performance for 5% sucrose, i.e., progressive ratio (PR) sucrose self-administration. Consistent with findings using other behavioral assays, both insulin and leptin significantly decreased the number of bar presses (62+/-7 and 76+/-8% of paired controls respectively), and the number of sucrose rewards obtained (87+/-4 and 91+/-4% of paired controls respectively), relative to within-subjects' control day performance on PR sucrose self-administration, whereas acute intraventricular cerebrospinal fluid had no effect. Rats fed a higher fat diet for 5 weeks were resistant to the effects of the intraventricular insulin or leptin, suggesting a central resistance to their action. Thus the findings of this study extend and support previous observations which suggest that neuroendocrine signals which regulate energy homeostasis in the CNS may also play a role in modulating reward circuitry, and specifically, food reward.

Analysis of Variance↗

PubMed2004

Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia.

We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls (n = 9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50 +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 +/- 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH.

Adrenocorticotropic Hormone↗

PubMed2003

Expression of simian immunodeficiency virus (SIV) nef in astrocytes during acute and terminal infection and requirement of nef for optimal replication of neurovirulent SIV in vitro.

As the most numerous cells in the brain, astrocytes play a critical role in maintaining central nervous system homeostasis, and therefore, infection of astrocytes by human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) in vivo could have important consequences for the development of HIV encephalitis. In this study, we establish that astrocytes are infected in macaques during acute SIV infection (10 days postinoculation) and during terminal infection when there is evidence of SIV-induced encephalitis. Additionally, with primary adult rhesus macaque astrocytes in vitro, we demonstrate that the macrophage-tropic, neurovirulent viruses SIV/17E-Br and SIV/17E-Fr replicate efficiently in astrocytes, while the lymphocyte-tropic, nonneurovirulent virus SIV(mac)239 open-nef does not establish productive infection. Furthermore, aminoxypentane-RANTES abolishes virus replication, suggesting that these SIV strains utilize the chemokine receptor CCR5 for entry into astrocytes. Importantly, we show that SIV Nef is required for optimal replication in primary rhesus macaque astrocytes and that normalizing input virus by particle number rather than by infectivity reveals a disparity between the ability of a Nef-deficient virus and a virus encoding a nonmyristoylated form of Nef to replicate in these central nervous system cells. Since the myristoylated form of Nef has been implicated in functions such as CD4 and major histocompatibility complex I downregulation, kinase association, and enhancement of virion infectivity, these data suggest that an as yet unidentified function of Nef may exist to facilitate SIV replication in astrocytes that may have important implications for in vivo pathogenesis.

AIDS Dementia Complex↗

PubMed2002

Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure.

The anatomic connections of the paraventricular nucleus of the hypothalamus (PVN) are such that it is ideally situated to modulate and/or control autonomic responses to a variety of stressors, including hypoglycemia. In our experimental model of hypoglycemia-associated autonomic failure (HAAF), a syndrome in which the counterregulatory response to hypoglycemia is partially compromised via unknown mechanisms, activation of the PVN is blunted (15). We hypothesized that this blunted PVN activation during HAAF may be sufficient to cause the impaired counterregulatory response. To test this hypothesis, we anesthetized the PVN with lidocaine during insulin-induced hypoglycemia in rats and measured counterregulatory hormone levels. PVN inactivation decreased indexes of the sympathoadrenal response (plasma epinephrine and norepinephrine) and the hypothalamic-pituitary axis response (ACTH). Inactivation decreased the peak epinephrine response to hypoglycemia by almost half (-42 +/- 6% from control; P = 0.04) and the peak norepinephrine response by 34 +/- 5% (P = 0.01). The peak plasma ACTH levels attained were suppressed by 35 +/- 6% (P = 0.02). Adrenal corticosterone and pancreatic glucagon responses were not impaired. This pattern of neuroendocrine response is unlike that previously seen with our HAAF model. Control infusions of lidocaine >or=1 mm anterior or posterior to the PVN did not simulate this neuroendocrine pattern. Thus it appears that decreased PVN activation, as occurs with HAAF, may be involved in specific components of HAAF (i.e., blunting the sympathoadrenal and hypothalamic-pituitary-adrenocortical axis response), but not in others (i.e., blunting the glucagon response).

Adrenocorticotropic Hormone↗