Biomedical subjects

L Middaugh

Publications and source records attributed to L Middaugh.

4 recordsLinked to original sources

PubMed2003

The noradrenergic system of aged GDNF heterozygous mice.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf+/-). Wild-type (Gdnf+/+) and Gdnf+/- mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf+/- mice in comparison with Gdnf+/+ mice. The reduced locomotor activity of Gdnf+/- mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf+/- mice. These findings suggest that the LC-NE system of Gdnf+/- mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life.

Aging↗

PubMed1998

SCID mice with HIV encephalitis develop behavioral abnormalities.

Severe combined immunodeficient (SCID) mice inoculated intracerebrally (i.c.) with HIV-infected human monocytes develop brain pathology similar to that in humans with HIV encephalitis. This includes HIV-positive macrophages and multinucleated giant cells, astrogliosis, microglial nodules, and neuronal dropout. These xenografts survive about 1 month. To develop a model of chronic HIV encephalitis and to assay the resulting behavioral abnormalities, we reinoculated SCID mice i.c. every 4 weeks for 3 months with either HIV-infected human monocytes (n = 5) or uninfected human macrophages (n = 4) or administered no inoculation (n = 6); these three groups were monitored for behavioral abnormalities. Tests of cognitive function in a Morris water maze 3.5 months after the first inoculation suggested that HIV-infected mice performed poorly compared with controls. Following testing in the water maze on days 4 and 5 of acquisition, motor activity of infected mice was reduced in comparison with that of controls. Retention of goal location when tested 1 week later was impaired in HIV-infected mice compared with controls. Histopathologic analysis of brains revealed significant astrogliosis and strongly suggested higher numbers of major histocompatibility complex (MHC) class II-positive multinucleated macrophages in HIV-infected compared with control mice. Thus, our preliminary studies indicate that SCID mice with HIV encephalitis develop behavioral abnormalities reminiscent of human disease. These behavioral abnormalities are associated with significantly increased astrogliosis, the presence of HIV, and probably multinucleated giant cells. These studies further support the use of this SCID animal model system for studies of the pathogenesis of HIV encephalitis and for drug interventions.

AIDS Dementia Complex↗

PubMed1997

The interactive effects of cocaine/gender on immune function in mice. An observation of in vivo acute cocaine exposure.

The present experiments used a mouse model including both sexes to study the impact of acute cocaine exposure on the function of four major immunocompetent cell types (T, B cells, NK, and macrophages). Cocaine hydrochloride, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice. Thymocytes and splenocytes were obtained 24 h after injection. Acute in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A in both thymocytes and splenocytes. However, the attenuated IL-2 production was only seen in thymocytes. These effects on T cells were greater in male mice than in female mice. The function of macrophages was also impaired by acute cocaine exposure; however, the impact was greater in female than in male mice. In conclusion, the effects of acute cocaine exposure altered the functions of immunocompetent cells and the effects varied with gender.

Animals↗

PubMed1989

Effect of central injection of phencyclidine on QNB accumulation and motor activity.

The purpose of the present research was to determine if central administration of phencyclidine (PCP) would increase the in vivo accumulation of the muscarinic ligand, [3H]quinuclidinyl benzilate (QNB) in mouse brain as has been reported after peripheral administration of PCP. Secondly, in order to provide a behavioral reference against which to compare any biochemical changes, the effects of peripheral vs. central PCP administration on motor activity were compared. When given into the lateral ventricle (i.c.v.) 20 min before QNB, PCP increased the accumulation of QNB in brain striatum and cortex, but not cerebellum. This finding replicates results of previous studies in which the drug was given i.p. The dose required to enhance QNB binding after central injection was, on a mg/kg body weight basis, approximately 10-fold less than that previously found necessary after i.p. injection. In contrast, PCP given centrally was markedly more potent in the motor activity tests than when given i.p. In addition, the behaviorally effective dose (0.4 microgram) was substantially less than that needed for the QNB change (25.6 micrograms). Therefore, though PCP was more active in both measures after central than peripheral administration, the changes in QNB accumulation cannot, at this time, be related to changes in motor activity.

Animals↗