Table 1.

Strategies for improving BDNF signaling in Mecp2 knockout mice

For detailed description, see the text. Abbreviations: TrkB, tropomyosin-related kinase B; nTS, nucleus tractus solitarius; mEPSC, miniature excitatory postsynaptic current; mIPSC, minature inhibitory postsynaptic current; PSD, postsynaptic density; LTP, long-term potentiation.

Approach		Effect	Evaluation	References
Genetics	Mecp2+/−;Cre93; CAGGS-BDNFstop	BDNF overexpression in postmitotic forebrain neurons	↑ lifespan; ↑ locomotor activity ↑ brain weight ↑ spontaneous firing (recorded in Lay V of  somatosensory cortex)	Chang et al., 2006
	Bdnf overexpression	BDNF overexpresison in neurons transfected with MECP2 shRNA or MECP2 R106W/TI58M	↑ dentritic length; ← dendritic branch points	Larimore et al., 2009
Pharmacology	BDNF application	Increasing BDNF content	↓ exaggerated EPSCs in nTS	Kline et al., 2010
	AMPKines	Increasing endogenous BDNF	↓ episodes of high breathing frequency but not ↓  higher frequency variability ↓ minute volume/weight but not ↓ tidal  volume/weight	Ogier et al.,2007
	LM22A-4	Activating TrkB receptor	↑ expiratory time; ↑ total breath duration	Schmid et al., 2012
	Fingolimod	Increasing endogenous BDNF	↑ locomotor activity; ↑ motor coordination ↑ straitum size ↑ frequency and amplitude of mEPSC; ↓ frequency  and amplitude of mIPSC	Deogracias et al., 2012
	Cysteamine	Increasing BDNF transport and secretion	↑ lifespan; ↑ locomotor activity	Roux et al, 2012
	7,8-dihydroxyflavone (7,8-DHF)	Activating TrkB receptor	↑ lifespan; ↑ locomotor activity ↓ tidal volume; ↓. irregular respiratory rhythms ↑ neuronal nuclei size	Johnson et al., 2012
	IGF-1	Activating the same downstream signaling as BDNF	↑ lifespan; ↑ locomotor activity ↓ cardiorespiratory irregularities ↑ brain size; ↑ spine density; ↑ PSD intensity ↑ synaptic transmission; ← cortical plasticity	Tropea et al., 2009
Physiology	Environmental enrichment (EE)	Increasing endogenous BDNF	↑ slightly in lifespan; ↑ motor coordination; ↑ motor learning; ↑ spatial learning; ↓ anxiety ↑ excitatory but no inhibitory synaptic densities in  primary somatosensory cortex; ↑ both excitatory  and inhibitory synaptic densities in cerebellum ↑ LTP	Lonetti et al., 2009