APOE status and its association to learning and memory performance in middle aged and older Norwegians seeking assessment for memory deficits

Abstract A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing.

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Methylphenidate treatment increases hippocampal BDNF levels but does not improve memory deficits in hypoxic-ischemic rats

Journal of Psychopharmacology ◽

10.1177/0269881120913153 ◽

2020 ◽

Vol 34 (7) ◽

pp. 750-758 ◽

Cited By ~ 1

Author(s):

Patrícia Maidana Miguel ◽

Bruna Ferrary Deniz ◽

Heloísa Deola Confortim ◽

Wellington de Almeida ◽

Loise Peres Bronauth ◽

...

Keyword(s):

Learning And Memory ◽

Memory Performance ◽

Memory Deficits ◽

The Novel ◽

Dose Response Relationship ◽

Stimulant Drug ◽

Attentional Deficits ◽

Hyperactivity Disorder ◽

Male Wistar Rats ◽

Learning And Memory Deficits

Background: Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet. Aims: We aimed to analyze learning and memory performance of young hypoxic-ischemic rats after MPH administration and associate their performance with brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus. Methods: Male Wistar rats were divided into four groups ( n=11–13/group): control saline (CTS), control MPH (CTMPH), HI saline (HIS) and HIMPH. The HI procedure was conducted at post-natal day (PND) 7 and memory tasks between PND 30 and 45. MPH administration (2.5 mg/kg, i.p.) occurred 30 min prior to each behavioral session and daily, for 15 days, for the BDNF assay ( n=5–7/group). Results: As expected, hypoxic-ischemic animals demonstrated learning and memory deficits in the novel-object recognition (NOR) and Morris water maze (MWM) tasks. However, MPH treatment did not improve learning and memory deficits of these animals in the MWM—and even disrupted the animals’ performance in the NOR task. Increased BDNF levels were found in the hippocampus of HIMPH animals, which seem to have been insufficient to improve memory deficits observed in this group. Conclusions: The MPH treatment was not able to improve memory deficits resulting from the HI procedure considering a dose of 2.5 mg/kg. Further studies investigating different MPH doses would be necessary to determine a dose–response relationship in this model.

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