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The expression of growth hormone receptor gene transcript in the prefrontal cortex is affected in male mice with diabetes-induced learning impairments
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
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2012 (Engelska)Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 523, nr 1, s. 82-86Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Previous studies have indicated that both growth hormone (GH) deficiency and diabetes are conditions associated with impairments in learning and memory processes. In this study, we investigated the effect of streptozotocin-induced diabetes on spatial learning in mice using the Barnes maze (BM). The expression of the GH receptor (GHR) gene transcript in areas of the brain associated with learning and memory were examined. The results indicated that the GHR gene transcript is up-regulated in the prefrontal cortex (PFC) of diabetic mice compared to controls. In addition, there was a significant correlation between the expression of GHR mRNA and performance in the BM during the acquisition phase in diabetic but not control mice. These results suggest that diabetes induces an imbalance in the GH/IGF-1 system leading to altered activity in the PFC and associated cognitive deficiencies.

Ort, förlag, år, upplaga, sidor
2012. Vol. 523, nr 1, s. 82-86
Nyckelord [en]
Barnes maze (BM), Cognition, Diabetes, Growth hormone receptor (GHR), Mice, Streptozotocin (STZ)
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-181862DOI: 10.1016/j.neulet.2012.06.050ISI: 000307619600017OAI: oai:DiVA.org:uu-181862DiVA, id: diva2:558020
Tillgänglig från: 2012-10-01 Skapad: 2012-10-01 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Ingår i avhandling
1. Growth hormone in the brain: Focus on cognitive function
Öppna denna publikation i ny flik eller fönster >>Growth hormone in the brain: Focus on cognitive function
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Cognitive impairments are an increasing health problem worldwide. In the developed countries, the average life expectancy has dramatically increased over the last decades, and with an elderly population more cases of cognitive impairments appear. Age, genetics, and different medical conditions such as diabetes mellitus, and substance use disorders may all contribute to declined cognitive ability. Physiological functions also decrease with increasing age, as does the activity of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Interestingly, both GH and IGF-1 are recognized for their neuroprotective effects and cognitive enhancement. The overall aim of this thesis was to investigate the impact of the somatotrophic axis (i.e. GH/IGF-1 axis) in rodents with cognitive deficiencies induced by diabetes or long-term drug exposure. For the first time cognitive impairments were characterized in diabetic mice using a spatial learning and memory task called the Barnes maze (BM). In diabetic mice, impaired learning in the BM was associated with decreased expression of the GH receptor (GHR) in the frontal cortex, a region important for e.g. working memory. Treatment with GH reversed certain cognitive impairments seen in diabetic animals. In rats treated with gamma-hydroxybutyrate (GHB), a significant decrease of Igf1 mRNA expression in the frontal cortex was observed. This observation may explain the impaired cognitive function previously seen following GHB administration. Furthermore, rats exposed to chronic morphine delivered in mini-osmotic pumps displayed memory impairments in the Morris water maze (MWM), an effect that seems to be associated with the composition of the N-methyl-d-aspartate (NMDA) receptor complex in the frontal cortex. In conclusion, the result strengthens the evidence for GH being a cognitive enhancer. Moreover, the result within this thesis identifies the frontal cortex as an important brain region, where gene expression related to the somatotrophic system is affected in rodents with cognitive impairments. The thesis especially emphasizes the importance of the local somatotrophic system in the brain with regard to cognitive function.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 79
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 227
Nyckelord
Growth hormone, central nervous system, cognition, morphine, gamma-hydroxybutyrate, diabetes, Barnes maze, Morris water maze, mice, rats
Nationell ämneskategori
Farmaceutiska vetenskaper
Forskningsämne
Farmaceutisk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-317305 (URN)978-91-554-9854-2 (ISBN)
Disputation
2017-05-05, B42, BMC, Husargatan 3, Uppsala, 09:15 (Svenska)
Opponent
Handledare
Forskningsfinansiär
Vetenskapsrådet, 9459Forte, Forskningsrådet för hälsa, arbetsliv och välfärd
Tillgänglig från: 2017-04-12 Skapad: 2017-03-15 Senast uppdaterad: 2018-01-13

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Enhamre, ErikaCarlsson, AnnaGrönbladh, AlfhildWatanabe, HiroyukiHallberg, MathiasNyberg, Fred

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Enhamre, ErikaCarlsson, AnnaGrönbladh, AlfhildWatanabe, HiroyukiHallberg, MathiasNyberg, Fred
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