Biomedical subjects

Steven J Henriksen

Publications and source records attributed to Steven J Henriksen.

22 records · Page 2Linked to original sources

PubMed2002

Loss of medial septal modulation of dentate gyrus physiology in young mice overexpressing human beta-amyloid precursor protein.

Mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show deficits in hippocampal-dependent spatial learning and hippocampal short- and long-term plasticity at ages preceding Abeta plaque deposition. We determined whether young PDAPP mice also exhibit alterations in septohippocampal function in vivo, which plays an important role in cognitive function. Electrical stimulation of the medial septum significantly increased neuronal excitability and reduced paired-pulse facilitation in the dentate gyrus. Medial septal-induced facilitation of dentate neuronal excitability was reduced in PDAPP mice. The inhibitory effects of medial septum stimulation on dentate paired-pulse facilitation were also attenuated in PDAPP mice. Young mice overexpressing hbetaAPP exhibit early abnormalities in neural circuits implicated in cognitive function that may play an important role in the more profound deficits observed in aged PDAPP mice.

Age Factors↗

PubMed2002

A novel electroencephalographic analysis method discriminates alcohol effects from those of other sedative/hypnotics.

Here we describe a mathematical and statistical signal processing strategy termed event resolution imaging (ERI). Our principal objective was to determine if the acute intoxicating effects of ethanol on spontaneous EEG activity could be discriminated from those of other sedative/hypnotics. We employed ERI to combine and integrate standard analysis methods to learn multiple signal features of time-varying EEG signals. We recorded cortical EEG, electromyographic activity, and motor activity during intravenous administration of saline, ethanol (1.0 g/kg), chlordiazepoxide (10 mg/kg), pentobarbital (6 mg/kg), heroin (0.3 mg/kg), and methamphetamine (2 mg/kg) administered on separate days in six rats. A blind treatment of one of the drugs was readministered to validate the efficacy of ERI analysis. Significant changes in spontaneous EEG activity produced by all five drugs were detected by ERI analysis with a time resolution of 5-10 s. ERI analysis of spontaneous EEG activity also discriminated, with 90-95% accuracy, an ataxic dose of ethanol versus equivalent ataxic doses of chlordiazepoxide or pentobarbital, as well as the effects of saline, a reinforcing dose of heroin, or a locomotor activating dose of methamphetamine. ERI correctly matched the 'blind drug' as ethanol. These findings indicate that ERI analysis can detect the central nervous system effects of various psychoactive drugs and accurately discriminate the electrocortical effects of select sedative/hypnotics, with similar behavioral endpoints, but with dissimilar mechanisms of action.

Acute Disease↗

PubMed2002

Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice.

Recent studies demonstrated that mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show age-independent and age-related deficits in spatial learning. We used behavioral and electrophysiological techniques to determine in young and aged PDAPP mice whether deficits in spatial learning also involve alterations in sleep-wake states, thermoregulation and motor activity. Consistent with earlier studies, young PDAPP mice exhibited selective age-independent deficits using spatial, but not random and serial strategies in the circular maze. Aged PDAPP mice exhibited deficits using all search strategies. The core body temperature (Tb) in young and aged PDAPP mice was significantly lower than in age-matched non-transgenic (non-Tg) littermates. During the dark period, the motor activity (LMA) was significantly increased in young PDAPP mice, but not in aged PDAPP mice. During the light period, young PDAPP mice showed a reduction in the generation of rapid-eye-movement (REM) sleep. In contrast, aged PDAPP mice exhibited a reduction in the amount of time spent in W and an increase in SWS during the light period. Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period. Our findings support previous reports indicating deficits in spatial learning in young and aged PDAPP mice. These data also suggest that PDAPP mice exhibit age-independent and age-related deficits in neural mechanisms regulating visuospatial learning, the total amount and the circadian distribution of sleep-wake states, thermoregulation and motor activity.

Aging↗

PubMedDate not supplied

Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons.

Prion protein (PrP(C)) is a constituent of most normal mammalian cells and plays an essential role in the pathogenesis of transmissible spongiform encephalopathies (TSE). However, the normal cellular function of PrP(C) remains unclear. Here, we document that mice with a selective deletion of PrP(C) exhibited deficits in hippocampal-dependent spatial learning, but non-spatial learning remained intact. mPrP-/- mice also showed reduction in paired-pulse facilitation and long-term potentiation in the dentate gyrus in vivo. These deficits were rescued in transgenic mPrP-/- mice expressing PrP(C) in neurons under control of the neuron-specific enolase (NSE) promoter indicating that they were due to lack of PrP(C) function in neurons. The deficits were seen in mPrP-/- mice with a homogeneous 129/Ola background and in mPrP-/- mice in the mixed (129/Ola x C57BL/10) background indicating that these abnormalities were unlikely due to variability of background genes or alteration of the nearby Prnd (doppel) gene.

Amyloid↗