Effects of Intraventricular Encapsulated Hngf-Secreting Fibroblasts in Aged Rats

1996 ◽  
Vol 5 (2) ◽  
pp. 205-223 ◽  
Author(s):  
Mark D. Lindner ◽  
Cristin E. Kearns ◽  
Shelley R. Winn ◽  
Beata Frydel ◽  
Dwaine F. Emerich
Keyword(s):  
Morris Water Maze ◽  
Basal Forebrain ◽  
Water Maze ◽  
Genetically Modified ◽  
Learning Task ◽  
Activity Levels ◽  
Aged Rats ◽  
Semipermeable Membranes ◽  
Age Related ◽  
Forebrain Neurons

Exogenous NGF administered into the central nervous system (CNS) has been reported to improve cognitive function in aged rats. However, concerns have been expressed about the risks involved with supplying NGF to the CNS. In this study, baby hamster kidney cells (BHK) genetically modified to secrete human NGF (hNGF) were encapsulated in semipermeable membranes and implanted intraventricularly. ChAT/LNGFR-positive basal forebrain neurons were shown to atrophy and degenerate with age, especially in cognitively impaired rats. The encapsulated BHK-NGF cells produced less than 10% of doses previously reported to be effective, but this was sufficient to increase the size of ChAT/LNGFR-positive basal forebrain neurons in the aged and learning-impaired rats to the size of the neurons in young healthy rats. The hNGF from these encapsulated cells also improved performance in a repeated-acquisition version of the Morris water maze spatial learning task in learning-impaired 20.6- and 26.7- mo-old rats. Furthermore, there was no evidence that these doses of hNGF impaired Morris water maze performance in the youngest 3.3-5.4 mo rats, and analyses of mortality rates, body weights, somatosensory thresholds, potential hyperalgesia, and activity levels, suggested that these levels of exogenous hNGF are not toxic or harmful to aged rats. These results suggest that CNS-implanted semipermeable membranes, containing genetically modified xenogeneic cells continuously producing these levels of hNGF, attenuate age-related cognitive deficits in nonimmunosuppressed aged rats, and that both the surgical implantation procedure and long-term exposure to low doses of hNGF appear safe in aged rats.

scholarly journals Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

2009 ◽  
Vol 102 (4) ◽  
pp. 2194-2207 ◽  
Author(s):  
David Murchison ◽  
Angelika N. McDermott ◽  
Candi L. LaSarge ◽  
Kathryn A. Peebles ◽  
Jennifer L. Bizon ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Cognitive Status ◽  
Cognitively Impaired ◽  
Aged Rats ◽  
Middle Aged ◽  
Cholinergic Basal Forebrain ◽  
Age Related ◽  
Forebrain Neurons ◽  
Firing Properties

Alterations in neuronal Ca2+ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca2+ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca2+ current recording with Ca2+-sensitive ratiometric microfluorimetry to measure Ca2+ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca2+ channel currents. However, Ca2+ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca2+ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca2+ buffering by cholinergic basal forebrain neurons may be important during aging.

scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Rat Model ◽  
Gut Microbiome ◽  
Water Maze ◽  
Single Injection ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Short Term ◽  
Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

Age-Related Vulnerability of Developing Cholinergic Basal Forebrain Neurons Following Excitotoxic Lesions of the Hippocampus

1994 ◽  
Vol 128 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Melanie A. Burke ◽  
Janice R. Apter ◽  
Bruce H. Wainer ◽  
Elliott J. Mufson ◽  
Jeffrey H. Kordower
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Basal Forebrain ◽  
Age Related ◽  
Forebrain Neurons

Increased Calcium Buffering in Basal Forebrain Neurons During Aging

1998 ◽  
Vol 80 (1) ◽  
pp. 350-364 ◽  
Author(s):  
David Murchison ◽  
William H. Griffith
Keyword(s):  
Basal Forebrain ◽  
Time Course ◽  
Smooth Endoplasmic Reticulum ◽  
Medial Septum ◽  
Diagonal Band ◽  
Age Related ◽  
Calcium Buffering ◽  
Intracellular Ca ◽  
Forebrain Neurons ◽  
Age Related Changes

Murchison, David and William H. Griffith. Increased calcium buffering in basal forebrain neurons during aging. J. Neurophysiol. 80: 350–364, 1998. Alterations of neuronal calcium (Ca2+) homeostasis are thought to underlie many age-related changes in the nervous system. Basal forebrain neurons are susceptible to changes associated with aging and to related dysfunctions such as Alzheimer's disease. It recently was shown that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of aged (24–27 mo) F344 rats have an increased current influx through voltage-gated Ca2+ channels (VGCCs) relative to those of young (1–4.5 mo) rats. Possible age-related changes in Ca2+ buffering in these neurons have been investigated using conventional whole cell and perforated-patch voltage clamp combined with fura-2 microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i), Ca2+ influx, Ca2+ transients (Δ[Ca2+]i), and time course of Δ[Ca2+]i were quantitated, and rapid Ca2+ buffering values were calculated in MS/nDB neurons from young and aged rats. The involvement of the smooth endoplasmic reticulum (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related increase in rapid Ca2+ buffering and Δ[Ca2+]i time course was observed, although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible buffering mechanisms were found to have roles in Ca2+ buffering, but they did not mediate the age-related changes. These findings suggest a model in which some aging central neurons could compensate for increased Ca2+ influx with greater Ca2+ buffering.

scholarly journals Correlations among central serotonergic parameters and age-related emotional and cognitive changes assessed through the elevated T-maze and the Morris water maze

AGE ◽  
2010 ◽  
Vol 32 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Luciana Oliveira ◽  
Frederico G. Graeff ◽  
Silvia R. C. Pereira ◽  
Ieda F. Oliveira-Silva ◽  
Glaura C. Franco ◽  
...  
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Cognitive Changes ◽  
Age Related
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