Differential effects of Phosphodiesterase 4A5 on cAMP-dependent forms of long-term potentiation.

cAMP signalling is critical for memory consolidation and certain forms of long-term potentiation (LTP). Phosphodiesterases (PDEs), enzymes that degrade the second messengers cAMP and cGMP, are highly conserved during evolution and represent a unique set of drug targets, given the involvement of these enzymes in several pathophysiological states including brain disorders. The PDE4 family of cAMP-selective PDEs exert regulatory roles in memory and synaptic plasticity, but the specific roles of distinct PDE4 isoforms in these processes are poorly understood.

Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation.

Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain.

Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation.

Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain.

Chemogenetic Enhancement of cAMP Signaling Renders Hippocampal Synaptic Plasticity Resilient to the Impact of Acute Sleep Deprivation.

Sleep facilitates memory storage and even brief periods of sleep loss lead to impairments in memory, particularly memories that are hippocampus dependent. In previous studies, we have shown that the deficit in memory seen after sleep loss is accompanied by deficits in synaptic plasticity. Our previous work has also found that sleep deprivation (SD) is associated with reduced levels of cyclic adenosine monophosphate (cAMP) in the hippocampus and that the reduction of cAMP mediates the diminished memory observed in sleep-deprived animals.

Endoplasmic reticulum chaperone genes encode effectors of long-term memory.

The mechanisms underlying memory loss associated with Alzheimer's disease and related dementias (ADRD) remain unclear, and no effective treatments exist. Fundamental studies have shown that a set of transcriptional regulatory proteins of the nuclear receptor 4a (Nr4a) family serve as molecular switches for long-term memory. Here, we show that Nr4a proteins regulate the transcription of genes encoding chaperones that localize to the endoplasmic reticulum (ER).

Pharmacological activation of Nr4a rescues age-associated memory decline.

Age-associated cognitive impairments affect an individual's quality of life and are a growing problem in society. Therefore, therapeutic strategies to treat age-related cognitive decline are needed to enhance the quality of life among the elderly. Activation of the Nr4a family of transcription factors has been closely linked to memory formation and dysregulation of these transcription factors is thought to be associated with age-related cognitive decline.